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

Thank you very much. Thank you for joining us on the afternoon session here. Really happy to have up here with me and the team from Iovance, specifically the interim CEO, Fred Vogt. Fred is going to make a couple of opening comments from the slides, and then we'll have a chance to do some questions and answers. And if you have a question, raise your hand. But I know I've got all the good questions. So I'll let you take the...

All right. Thanks, and thank you for the invitation. This is fantastic to get to see everybody in person. I'll be making some forward-looking statements today, so please take a look at the disclaimer. I'll just give you a brief summary of Iovance really quickly, and then we'll go to the fireside chat. Here's Iovance by the numbers. We're the global leader in developing innovating TIL therapies, tumor-infiltrating lymphocyte therapies, which are polyclonal T cells. I'll talk a little bit more about that as we go. We've treated more than 500 patients at Iovance. We've got a 90-plus percent manufacturing success rate, and we've got a 22-day proprietary process for manufacturing TILs. It is the fastest in the industry right now and is a core part of our clinical program. We've got 6 active clinical trials, many of which have multiple cohorts or arms to them. We've got 5 indications in the clinic, 4 solid tumor and 1 hematological cancer. Got 1 breakthrough designation and 1 RMAT designation from the U.S. Food and Drug Administration and 3 Phase Track designations from the agency as well. We have $560 million in cash as of the last quarter report, 40-plus international patents and U.S. patents and 400-plus employees, and this is just a short list of some of our collaborators. We couldn't get them on here, but some of the -- our collaborators are very important to us. They include the National Cancer Institute and Dr. Steven Rosenberg, laboratory, who worked with very closely, MD Anderson, Moffitt, Yale and Selectus, particularly for gene editing. This is a quick shot of our pipeline. I won't talk about everything on here, but I'll give you some idea what's going on with our pipeline, just a little bit of formatting issues on this thing, at least from where I'm standing. At the top, we have our monotherapy pipeline, including our top most trial, which is our Cohort 4 of our C-144-01 study. I'll talk about that in a minute as well as Cohort 2. That's our pivotal study and the study we intend to use for our BLA filing in post anti-PD-1 melanoma. And then we have some other monotherapy indications up there, including cervical and lung. Then with the green bars, we have our TIL combinations where we combine TIL therapy, typically with pembrolizumab, but also with nivo and ipilimumab. We've got a PD-1 selected TIL product in the magenta colored bars there as well as the Gen 3 product, which is a 16-day manufacturing process that's our sort of cutting-edge short TIL manufacturing process and multiple indications. We've also got a PVL or peripheral blood lymphocyte therapy. That's in sort of the purplish color there. That's in CLL, chronic lymphocytic leukemia. We've got a PD-1 in activated TIL, and that won't get a little bit messed up there, but there's aqua blue bars there. That's our first gene edited TIL product, and it should be the first gene-edited TIL product activated in a multicenter study, hopefully very soon. And then finally, we have our own IL-2 analogue. We use IL-2 or aldesleukin as supportive part of our tumor infiltrating lymphocyte supportive regimen. I want to quickly cover some of the melanoma data highlights. First, the market for melanoma in the United States and around the world. 100,000 diagnosis in the United States, almost 8,000 deaths a year, tremendous opportunity right now for a line of therapy that will come after patients have failed anti-PD-1. That door is completely open. All it's available right now is down in the lower right corner, chemotherapy, typically dacarbazine with a very low ROR and short overall survival of only 7 to 8 months of those patients. So there's very limited options. You have to progressional checkpoint, of course, for BRAF mutant patients, the BRAF and now more commonly the BRAF MEK combination. This is our Phase II study design for our melanoma trial. You can see the 2 light blue cohorts, Cohort 2 and Cohort 4. Those are the 2 cohorts that relate to our BLA filing. Cohort 4 is the pivotal cohort, Cohort 2 is supporting. We started the study. The primary endpoint is efficacy by objective response rate by RECIST 1.1. We started the study and -- back in 2019, enrolled it very quickly, enrolled it under a year. In May 2021, we published Cohort 2, which was the earlier cohort. In May 2022, just last month, we put out top line results from Cohort 4 and Cohort 2 as read by independent review committee, which is something FDA wanted us to do. Cohort form particular was read by a prospective IRC. That was an FDA requirement, and we have an anticipated BLA submission of August 2022, which is just around the corner here. The results of the study, we met our primary criteria in the sense that we rejected the no hypothesis of 10%. The overall response rate in Cohort 4, which was 87 patients was 29% with a 10.4 month median duration of response at 23.5 months of median study follow-up. Cohort 2 by IRC was 35% ORR, median DOR was not reached with 36.6 months of median study follow-up. And when we pull -- now on the left-hand side of the slide, this is what the FDA really is looking for, they're looking for the 2 cohorts independently, and that's how the clinical study report and the BLA submission goes. On the right-hand side of this slide is what the physician community thinks and sees. That's 153 patients pulled together, same enrollment criteria for the study. And that result when you pull it all together, is 31% ORR, median DOR not reached to 27.6 months of median study follow-up. Importantly, Cohort 4 patients had more advanced disease than Cohort 2 patients, and that's illustrated by 3 measurements that we have in the bottom right here. One is they had about twice the duration of median prior anti-PD-1 therapy before they came on a trial, cumulative median prior anti-PD-1 therapy. They also had higher -- that we had a higher percentage of patients with elevated LDH in the study. We had about 60-some-percent as opposed to 40% between Cohort 4 and Cohort 2, respectively. And then finally, the patients in Cohort 4 had a greater number of lesions at baseline to those in Cohort 2, significantly greater. So we saw some sicker patients, but the therapy still work quite well, and we've got some good durability. Durability is further illustrated on this slide where we show that 44% of responders still were in response at greater than 12 months after -- this is the time of the data cut. At the time of the data cut, the longest respond that was 26.3 months. Now if we look at the data today, we still have many, many patients in response and those numbers will go up from that, but that's where we were at the time of the data cut. Also, these patients were heavily pretreated. We had 3 median prior lines of therapy in both Cohort 2 and Cohort 4. And then prior anti-CTLA-4 use was very high in Cohort 4. We had 83% of the full analysis set, which is essentially the 87 patients, seen prior anti-CTLA-4 ativolimumab and then 55% actually sold a combination of nivo/ipi or PD-1 anti-CTLA-4. As we get ready for commercial, we're focusing on our treatment centers around the country. The stars are our clinical sites and the blue dots are our treatment centers that we're aiming to engage with to launch the lifileucel product in metastatic melanoma and post-PD-1 melanoma. We are targeting centers that have at high patient volume, NCCN status KOLs. We work with a ton of KOLs in this business, and we'll probably end up talking more about them as we go through Mike's questions. We're looking at existing cell therapy centers and bone marrow transplant centers, and we're also looking at our clinical trial sites. We're trying to prioritize top accounts because we know the majority of demand comes from certain large centers around the country, and we're also trying to prioritize community referrals because a lot of melanoma patients are seen in the community setting. And with that, go to the far side chat, I guess.

Thanks for that overview. That was fantastic. And I would love to hit on some of the things that have come up recently. One is the disclosure of the Cohort 4 data 29% response rate, duration of response, 10.4 months and somehow the market seem very disappointed by those results, I guess, mostly on duration of response. What is your response to the duration of response? And how do you respond to the market with that result?

Why don't I take the market part may you can talk about the durability. So I think there's a disconnect between the market talking -- I'm sorry about that. Is it better? I think there's a disconnect between the market and the physician community right now. And I think we can say that confidently coming back from ASCO and having talked to more than 50 KOLs in the melanoma space. The KOLs we need in this data is very durable. It's immunotherapy data. It has a long tail on a capital Myer plot. We haven't put all the data out yet, but now we're putting a little bit more out and clean the 44% number to show people that we do have.

That was new.

Response we put that out right after the very quickly after the disclosure. So the market reaction, yes, they looked at the number. They focus on that number. They focus on the ORR having gone down. Remember, it's a point estimate, it's well within the confidence interval, and they focus on the durability. Our message to the market is the durability is still there. Now the physician community, Hari can speak to a little bit more about his experience at ASCO and what they think about the durability, why don't you tell them?

Yes. So as a medical oncologist, whenever you have a refractory solid tumor treated with the cell therapy and a bunch of patients achieving long-term durable responses, that is a big win. And that's what we heard from the KOLs as well. What Cohort 4 informs practice for most of them, most of the melanoma physicians, almost all of them actually who talk to us and you can also -- and as was discussed in an education session at ASCO was that Cohort 4 informs that the patients who had rapidly progressing disease as evidenced by higher LDH or bulkier disease with multiple sites of lesions or who underwent what we call PD-1 recycling. They were failing a PD-1 agent and turned to a second PD-1 agent third 1 agent in combination with perhaps. Those patients, basically, that's a practice that they wouldn't do if this were available commercially. They would recommend that TIL is now firmly in the second line space, true second line space. Our study aim to enroll patients who have just PD-1 exposure and BRAF exposure. But our median prior lines was 3, suggesting that we had a lot of patients who were getting multiple more lines then. And this -- we didn't select for LDH or select out for a number of lesions or et cetera. We let anybody come in. And everyone was asking me, why would you think Cohort 4 enrolled sicker or more advanced patients, not really sicker, more advanced patients. The answer is that Cohort 2 was when TIL was coming in as a new therapy for patients and physicians and patients who are unsure about what this would do. By the time Cohort 4 has started, we had actually a lot of data points out in the literature as well as in meetings with durable responses and patients sought us out. Essentially, sicker patients came patients came having been on PD-1 trying to get to TIL and physicians were more likely to put them on. And that's, again, the speed at which this trial enrolled, it's enrolled fully all 87 patients were enrolled between March 2019 and January 2020, in like 9 months filling up a 87 patient cohort.

Just to be clear, prior lines of therapy, the median number, average number, whatever you want to say, if you look at the baseline demographics, the median lines are greater than Cohort 2?

Double, actually.

Double. And why you believe -- or this way, going back to the 10.4%, it's interesting because immuno-oncology is particularly attractive, driven by a proportion of patients have a very long tail. The median gives you the middle 50th percent person. So it can be misleading up. Gilead very much explained that, too, because they just went through tropics explain that as well. But here, we don't get to see the curve, whereas Gilead, you get to see the curve. So when you talk about the median being 10.4 months, and I think you just disclosed 44% of people or greater than 12 months, I can start to visualize or make a chart you telling me that if I stack that swimmer plot next to Cohort 2, you think they're generally identical. It's just that the first 50% is more this way, but the other 50% is still going out very far. Do you think there nearly identical? Is it a median problem?

If you're thinking of the Capital Myer.

Speak into the mic.

Sorry. If you think in the Capital Myer curve, you would have a long tail. It's just a little bit lower for 4 than it is for 2, okay? If you're thinking of swimmer plots, which is what we'll put out is more relevant for this type of study of single arm study, you're going to have in the cohort 2, you're going to have -- the swimmers are going to look like they're more in line, and they're swimming out far whereas in cohort 4, they're going to look like they have like a detonate, where they -- right in the middle -- patients one way or the other, you reach median, right, the patient...

And you think that those are the sicker patients. So you have this like going out and then right at the 50th percentile part because there's the proportion of people who are sicker that they obviously had a shorter response, but the other 50% of people who are more similar to Cohort 2, they continue to go out far just like in Cohort 2.

And we have many responses still ongoing in Cohort 4 today actually even now, which is well past the FDA cut. So we'll get more out. We're coming to the conferences at the end of the summer on this. We're trying to get as much out as we can in support of our commercial proposition, but we have to communicate really effectively to the medical community now because they're the one writing the scripts ultimately for this. At ASCO, we showed the data to a lot of KOLs because they're under a contract with us 1 way or the other, okay. 54 of them, all 54 were positive, 49 in the United States. They all said they would write scripts. In fact, 1 of them, Allison Warner changed her slides and changed our educational session at ASCO in front of 1,000 people to include lifileucel as the next therapy after PD-1. We can get you the slide of your interest.

I would love to see those slides, okay. Just the session on melanoma.

Cell therapy for solid tumors.

Adoptive cell therapy for solid tumors. The 3 speakers, 2 of them are on TIL.

Next steps, I don't want to spend too much time on the extra data because the data is there, and it will eventually be presented. But the next steps, obviously, are meeting with the FDA in July and preparing to file. What are the things that have to happen at the July FDA meeting? What are the key things? And is there any risk to any of that such that you wouldn't be filing in August?

Well, what we're focusing on for July is essentially formality question. So we're asking literally, they're kind of silly, but we're asking questions about how to format tables and how to link sections together to document. All the potency assay stuff has been, we think, addressed. There is always a risk, but we think it's been addressed. We've got an FDA feedback, it was positive. We spoke about that. And the clinical data is not really something that we're going to discuss at the pre-BLA meeting. That goes into the CSR as part of the filing. FDA has seen it. They know what the top line is. They know before the market new and we're moving forward with that. So what we anticipate happening is we have a pre-BLA meeting in July, we have a discussion largely about the formatting of the BLA and some of the stuff is important. It actually is important, but it's more technical in nature. And then we have the BLA submitted in August. That's where we are right now.

Okay. And as you go through that, obviously, I presume you expect a prior review. You're talking about a PDUFA in the spring, right? Are there -- is there any other things that you need to think about? Obviously, an inspection and approval of the factory. What are the other things that sort of are -- we need to think about?

Yes. There's -- well, there's a ton of thing. This is what we spend most of our day doing and 400 people spend most of a day doing. Getting ready for FDA inspections, getting this document in order being prepared so that nothing goes wrong during a pre-licensing inspection that all the CROs that we're using, all the supply chain partners that we're using [indiscernible] inspection you name it, getting our own people trained up to the top absolute top level. We've got a lot of good people internally with a lot of good FDA inspection experience, and we're turning that loose. And then of course, we have to complete the filing and complete all the -- it's just thousands and thousands and thousands of pages of documentation goes into BLA and tons and tons of reports that sit behind a BLA that FDA can show up and look at. So all that's what's going on internally right now. I think about it, I had a lot of years working in Glaxo, we went through a lot of, we used to call them, PAIs back then, they were called preapproval inspections. Every one of them was a lift, a heavy lift, but we've learned where you just -- you have to exercise before you make that lift, and that's what we're doing. So we're getting ready to get...

Well, look, it's an autologous therapy. It requires custom manufacturing. It is at a new factory. You did host a tour there and hosted folks through there. And by definition, people are nervous about that. And some of this stuff as we've been watching through FDA has been challenging to get this stuff done in a COVID environment or just a cell and gene therapy environment, which I might add has been challenging for people, too.

That's right. That's right. We have a good head of Regulatory Affairs. We hired a guy Raj Puri from the FDA. He was the Director of the Vision and Cell Gene Therapy.

You clarify that who you hired, and what's he'd been working on?

Yes. So Raj is our Head of Regulatory Affairs. He's not here today. Unfortunately, he's on vacation this week, but he is...

He's working.

He's working, yes. Of course, he is. He is -- he was the former Director of the -- essentially all the cell and gene. The division oversees all the cell and gene therapies at the FDA. He had jurisdiction over several thousand INDs and he signed off on all the CAR-T products that were approved. He's got a wealth of experience. He's also got wealth of contacts, and he's building an even stronger regulatory affairs group, which helps our quality group, make sure that everything is in order and our manufacturing group, make sure that everything is in order and our external manufacturing group and so on. So we're -- this is something that -- I mean, if you could come inside Iovance and see what we do all day, this is what we do all day, getting ready for this stuff.

Look, I don't -- I didn't spend a lot of time on this before, but look, this person was a key person at the cell and gene therapy division there, reviewing all that stuff. The same people you're interacting with -- the people he worked with.

That's correct. He's also one of the thought leaders at FDA on potency assays. He was -- had a lot to do with the 2011 guidance on potency assays that the industry follows today. And with 30-some years of experience at the FDA seeing all the cell and gene products come through already, he's got a lot to offer. And that's -- and then he has a team of more than 10 people now, which are specialists in this area, too.

Okay. One other sort of thing that I noticed with priority reviews single-arm open label state is FDA often requiring some form of confirmatory study, progress through in consideration to one. Some people have done it, post-marketing or agree on one post marketing and may people like KRAS and all these other drugs have been trying to do it and rushing to do it before the thing is approved. What is the FDA said about a confirmatory study?

So FDA says you have to have it up and running at the time of approval and they want it running as soon as possible because they're worried about this phenomenon of people saying they're going to run these studies and they're not getting them started and getting their accelerated approval. We've heard that from FDA repeatedly in multiple meetings on different products, too. So it's definitely -- part of the reason we announced the Phase III study back a few months ago is because this is where we're headed. We're going to have this Phase III study up and running in time for the approval, so that can be our confirmatory study if needed. That said, it's important to note, you've heard from Raj, on some of our calls, actually, I think it was only on the calls with you. We do think there is a reasonable chance of getting a full approval here given that we have 153 patients worth of data, the size of the data set, the fact that we ran 2 cohorts that were both IRC read. So there is a chance that this study will not need to be a confirmatory study where we will get a full approval. And then the study that we're running would become a study for looking at a supplemental BLA for a label.

Yes. I had missed that slide, but that's the first-line study. What was the...

Yes we haven't -- so we haven't disclosed the details yet because we have to talk to FDA, but where it's planned to be a frontline study, take a look at Cohort 1A, it's called 1A. It's basically pembro plus TIL. We're looking at about a 70% response rate right now with good durability. The data is in our corporate deck. We can get you a copy of it. That data and plus we know internally and what we know from Steve Rosenberg's work is informing our decisions for that confirmatory trial that might not turn out to be a confirmatory trial might just be a trial.

I see. So you've got one plan that's definitely cemented. You want to do that, timing of when to start it. We'll push you harder later on unless you've committed to that. But...

Look, we're not going to know we have full approval until the day the BLA gets approved. So it's going to be up and running regardless. Put it that way.

It will be up and running before that...

Yes, whether it's a confirmatory trial or just a trial, we'll -- you can rebrand it afterwards.

Last question in the last 45 seconds, we have a balance sheet. You talked about how you have over $500 million of cash. Jefferies model says you're burning a few hundred, a couple of hundred, whatever it is per year. you have a milestone coming up, which is an acceptance fleet of the BLA. And then ultimately, we execute towards an approval. So talk to us about your comfort on the balance sheet? Or how would you be opportunistic -- to raise money?

Yes, we've guided into 2024. That's our official guidance. We're burning well under $300 right now, and we can keep that burn under control. Right now, the market obviously as the conditions are quite poor for equity financing, as you know, but there's all sorts of alternatives if we need it. And again, we think we're going to have catalysts prior to that coming to pay us anyway...

Like the regulatory stuff. How about more data like...?

Data potentially. And then, again, we've already made it clear that we'll be talking a lot about Cohort 2 and Cohort 4 at the fall conferences, including subpopulation analyses primary refractory patients, patients after prior lines or nivo, that kind of stuff.

Okay. Thank you very much for the update. We appreciate it. We look forward to the milestones this year.

Yes, thank you. We appreciate the invite.