I like that question.
You like that question?
Yeah.
Okay.
'Cause I can talk about iCTC, why we're doing.
Okay, why, yeah. That's why we have a big investment with it.
One, two.
Did we get the go-ahead?
Yep.
One, one, one. One, two.
Are we good?
Okay.
We're good.
Good afternoon, everyone. Thanks for being with us today for the Baird Global Healthc are Conference. My name is Colleen Kusy. I'm one of the senior analysts covering biotech here at Baird. It is my pleasure to have with me management from Iovance Biotherapeutics, including Jean-Marc Bellemin, CFO, Igor Bilinsky, Chief Operating Officer, and Dr. Brian Gastman, SVP of Medical Affairs. Thank you all for being with us.
Thank you.
I kind of assume everybody's probably familiar, but maybe just for those who are not, just a brief company overview, and then we can dive into some Q&A.
Yeah, let me do that briefly. So as you all know, we launched our first drug little over six months ago, February 2024. AMTAGVI was the first cell therapy in solid tumor with the indication of, you know, pre-treated advanced melanoma patient. The launch is going very well. We'll certainly address that during the question. The goal of AMTAGVI is potentially to address 20,000 patients worldwide, so there is a huge potential there, and again, we are trying to expand. So now we launch in the U.S., but we will be expanding in Europe soon. We filed in Europe by the end of Q2, and we have now received, actually, from the EMA that they will review the dossier. So we are planning to launch in Europe in 2025.
More to come on the exact date later. We are also going to file in the U.K., MHRA, by the end of this year, in the Health Canada, and Australia in 2025 . So a lot of geographical expansion in the current indication. Beyond that, we have two registrational clinical trial ongoing, one in a first-line melanoma patient that you know will be able to expand our current indication for AMTAGVI, and also one in the pre-treated and non-small cell lung cancer patient. We have some clinical trial happening and underway in endometrial cancer patient, and from a you know life cycle management, we have a lot of different you know future treatment paradigm being either in the clinical stage or soon to be in clinical stage. So.
Fantastic.
There you go.
Lots going on.
Yeah.
So maybe I'll start with a topical question I've been getting a lot so far today. Your EVP of Commercial, it was announced yesterday afternoon, had departed to go to a different company, if there's kinda any kind of color you can provide on that transition.
Yeah, no. Thanks for asking the question. Happy to address that. So yes, Jim decided to join another company. You know, we wish him the best. I mean, we are not commenting too much around his departure, but we wish him the best. So Jim has been, you know, critical in helping us to build a team, to build the infrastructure, and now we are in the launch mode, and we are demonstrating everything is running really well. We of course maintain all the guidance and everything. Nothing has changed there. So we wish him the best, and we'll benefit from that to actually upgrade the position to a chief commercial officer.
Mm-hmm.
Recruitment in that is underway, and I can just share with you, we have already quite good candidate.
Mm-hmm.
We're excited about this opportunity.
Okay, great. And let's dive into the AMTAGVI launch. So, yeah, recently approved, and in February of this year, launched, and so kinda talk about some of the initial patients that you're seeing, kinda how heavily pretreated and how that's gonna change over time.
Sure, I can answer that. So early on, we knew there would be some patients that were waiting for this to happen, and we definitely did see that. What we've come to realize, and I think we sort of knew, but not to the extent we now know, is the importance of patient selection and that there's a window of opportunity to really achieve the ability to make great product in time and then get great responses for patients. And so, what we've seen is a natural maturation of centers realizing that on their own, plus the fact that we're able to process information from all the centers and then reapply that back to them. So we've actually accelerated that education process as we learn it.
And the other thing I would say is that we've seen some centers really get out ahead of this and do incredibly well on all fronts, and we've really looked at them as models of what to apply to the other centers. So I'd say overall, while the early days, those patients were heavily pretreated, today, what we're seeing is it's starting to really fall in line with our label, and I think with that, the successes that will come with that.
Great. And can you speak to the manufacturing success that you've had so far, and what your expectations are for this quarter and the quarters ahead?
So manufacturing experience, commercial has been consistent with our clinical experience, nothing unexpected, and Brian and his team have been doing a fantastic job making sure that the ATCs do the tumor procurement properly for manufacturing and share the best practices, educate them, because that's very important. We've been learning a lot about the little details over the past months and implementing that into practice to make sure that the success rate remains high and increases going forward, and we're seeing that in practice.
Great. And, you know, some of the contribution both there can be your product that isn't able to be manufactured, but then there's also patients that might progress before they are able to receive the TIL product. So how do you, how do you shrink that number of patients that progress before being able to be treated with TIL?
I think it goes back to what I said previously. It's patient selection, patient selection, et cetera. I mean, by doing that, you reduce the risk that they can't wait. You optimize their own immunology, which helps us to get more cells for great manufacturing. And ultimately, those type of patients, just as a clinician, are the ones who likely also benefit when they actually get the therapy. So I think that's a large part of it. Then there's other aspects, too. We have looked at many ways to constrict down the whole process, including working with ATCs to have them do things in parallel, like scheduling surgery, et cetera. We're seeing single case agreements occurring sometimes in days, not even weeks anymore. It's still exceptions, but we're trying to make that the norm. And then there are other aspects.
So for example, centers do lymphodepletion on certain days, so we're working very hard to harmonize the end of our manufacturing QC with them being ready, whether they're starting lymphodepletion a little bit before they get the product or literally the day they get the product, so that there's literally no delays, and with all that, we're starting to see glimpses of a future where we're going to cut this down even further than what we've told you in the past.
Great. And maybe back on the manufacturing side, there was the BIOSECURE Act has been in the news the last couple of days, and you have your partner, WuXi. Can you kind of comment on how that might impact your relationship with WuXi?
Mm-hmm.
A nd how that impacts your supply?
So short answer, we don't anticipate any impact to the commercial supply of AMTAGVI to patients or clinical supply to clinical trials, in part because way before BIOSECURE was even a concept, we knew that we had to have control of our manufacturing capacity. That's a core capability for us at Iovance, and we invested in building our own manufacturing facility, the Iovance Cell Therapy Center in Philadelphia.
Mm.
That's one of the largest cell therapy facilities in the world, the only one dedicated to TIL manufacturing, and it has capacity that's built to provide TIL for more than two thousand patients annually, and with the build-out of the shell space in the same building that's underway now, up to more than five thousand patients annually. WuXi is an important partner for us, but we have full control of our destiny and fully own the manufacturing that we need to own to provide AMTAGVI to patients for the foreseeable future.
Great. And let's talk about the ATCs. So you've onboarded 50 already. You've guided towards having 70 on board by the end of the year, the broadest launch that we've seen so far in a cell therapy. So why, why go so broad? And kind of what's been your relative experience so far?
Yeah, well, go ahead.
Oh, no, go ahead.
So we know from CAR- T experience that the top 10 centers generally do about half of all CAR- T in the United States, even when they have over 100 ATCs, and about 40 do about 80% of all that effort. And so we expect the same thing to occur with us as well. So number one, we don't know which are the 40 centers, and so you've got to pick more than that. And we've really picked not only the top centers you would think of from a cancer volume, melanoma volume perspective, but also having cell therapy operational excellence. In addition, we're very cognizant of being, having to give as much access to patients as possible.
Right now, every patient in the United States, at least in continental United States, has about a 200-mile or less drive to get to the authorized treatment center. We want to get that under 100 miles. By strategically placing authorized treatment centers in these 70, the goal is to both capture the best centers and help cultivate them to be at the level we see in CAR- T very quickly, not waiting as long as we saw other launches to get to that point, plus to get the access now, because there are patients who just simply will, I mean, it's sad to say, really would not take therapy if it takes too much effort to get there, and we're making sure that that's not going to be a barrier for them.
Great. Yeah, as you've been out in the field, what, what's been kind of some of the main pain points or bottlenecks that these centers have been facing, and how can you apply those learnings to other centers?
Well, you know, I can't say there's been a lot of actual pain points in the sense that they weren't surmountable. Pretty much everything that we've seen are things that have been easily and quickly addressable. You know, you'll hear things about time to get a slot, but a lot of that turned out to be the fact that centers were saying: "Well, I only operate two Fridays a month, and you have to give me the next slot." And I'm like, "Well, you know, but we have other days open." And then there was issues of slot availability, and then we start to get them to be more flexible and realize the bigger picture of what we're trying to accomplish, and how we're not really reinventing the wheel.
Slot utilization management is something we're the seventh company to do. There's nothing magic about this. And then you throw in on top of that, the fact that we have this great case manager team that white gloves the service, that can literally take a patient that's scheduled, you know, initially penciled in for some weeks out and pull them in, 'cause it happens reliably.
Mm.
We really don't see problems. We immediately fix them. I haven't seen anything that has been unsurmountable, and when one center does talk in those terms, we've been able to use other centers' ability to overcome those problems or not have them at all as a testament and as an example of what they can do, and they've used that to-
Yeah
To deal with them.
Great. And so moving to Proleukin sales, I think that was kind of a bit of a positive surprise to everybody, and the 2Q print reflected a lot of patients' worth of Proleukin sales. So maybe touch on the average cost of Proleukin, remind us and kind of how you're seeing distributors and centers order, their ordering patterns.
Yeah, so let's talk about that. So Proleukin WAC in the U.S. is $5,551 per vial, and we from the clinical setting, we have seen that generally it's around 15-18 vials per patient. So we talk and commented around the revenue being $80,000-$100,000 per Proleukin patient. But you have to realize Proleukin is also outside the U.S. We are selling outside the U.S., yes, at a lower price, but we're also selling even in the U.S. at third party or other companies because we are the only supplier for Proleukin. So there was some stocking in Q2. We have been transparent around that because this is the starting for us to use specialty distributor and revenue is recognized at the moment.
We sell to those specialty distributors, so a little bit stocking, but they are already reordering. So we know there is a demand out there, and we have said majority of the demand is certainly AMTAGVI related.
Great. And so, yeah, you did $18 million in Proleukin sales in 2Q. Can you help us understand the trajectory of Proleukin revenues from here? Do you expect that to grow quarter- over- quarter in 3Q, or what, what are the dynamics expected there?
Yeah. Based on what I just commented around the, the revenue source of Proleukin, I think we can expect flat, directionally flat or increasing over time. Increasing is particularly based on the fact that AMTAGVI number of patient will increase, so we could expect over the next few quarters an increase on the Proleukin revenue.
Great. And so one thing I think is important for all of us to understand, obviously, this is the first time you're setting guidance. You've set guidance for the first time on 2Q. Just trying to understand what your approach to guidance is and how we should be thinking about this guidance. You know, is this really realistic? Do you take a more conservative approach? How do you think about setting guidance?
Yeah, so just to remind everybody, what we have said is Q3 will be $53 million-$55 million. We expect $160 million-$165 million for the full year 2024, and $454 million-$475 million next year. So why are we confident to be able to go out there and talk about those guidance? It's because we see the launch dynamic, how the ATCs are bringing the patient, what is happening in terms of the manufacturing slot scheduling, what is happening in terms of the patient selection, better outcome there. So we know and we are confident that the trajectory is set already. We are, of course, increasing to 50 ATCs. We'll have 70, as we just discussed, by the end of this year.
Don't forget also the Proleukin revenue I just commented. So altogether, we are really confident about those numbers.
Okay. And how does your general approach then apply? Like, what are some of the big assumptions that we have to make around the 2024 and 2025 guidance?
Yeah, I think it's about the demand. I mean, first of all, it's the number of AMTAGVI out there. We talk about, you know, 8,000 patients in the U.S. Again, it's the number of ATCs progressing, the number of AMTAGVI patients. We have seen this increasing over time, and there is no ceiling for the moment. So the fact we'll go to 50, the fact we'll go to 70, that's one of the most basic assumption for us for the guidance. On top, again, of manufacturing success, manufacturing slow scheduling, all the patient selection and experience.
Great. And so you did provide guidance on 70% + gross margins over time. You know, what gets you from where you are today to 70% + margins?
Yeah, another proof we are confident about something. I mean, gross margin of around 70% on the future years. If you look at what we commented for Q2, we are in the product gross margin overall at 26% already. So yes, there is a gap, but we know that we will improve on AMTAGVI. We have a control on cost and quality from iCTC. We will improve on the process optimization, automation, so there is a lot there. There is, again, same thing on the patient selection and optimization, where we can limit the dropout. So a lot that can happen on the cost of sales that we can improve over time.
Great. And you've also provided some cash burn guidance. So maybe kind of remind us what that is and your projected cash runway.
So cash available at the end of almost end of July was $450 million. This will go on to early 2026, because we want to account the fact that we, of course, are showing that we have at least $610 million worth of revenue until end of 2025-
Mm-hmm
With a reasonable margin out of that. But we also have a lot of investment plan for manufacturing and increasing capacity to meet the demand. So altogether, again, we have enough cash until early 2026.
Great. And now, shifting gears a little bit on the clinical side to the TILVANCE-301. You had some, you know, really, I think, exciting data coming out of ASCO this past year.
Mm-hmm
30% complete response rate in the frontline setting. How should we think about the enrollment of TILVANCE-301 and the timelines there?
Yeah, I think it's first and foremost, most important to understand that we are extremely aligned with the FDA. The floor of this trial is to get a full approval for AMTAGVI, and the ceiling is to disrupt the front line field, and really to bring the promise of TIL therapy to all melanoma patients. When you think about the accrual, the fact is that we need to make sure that our on pace-ness, our well underway-ness, if you will, is what the FDA defined it to be, and we are. And if you look, we're open in 40 centers in 10 countries. We're looking at another 60 centers, which would be a total of 18 countries. So our ability to get where we need to be is absolutely on pace.
We don't see any issues there, and we're definitely in contact with the FDA constantly to make sure that we are keeping up our end of the deal, and we are. We're seeing them come in, and it's definitely moving along nicely.
Mm-hmm. Great.
So that, I hope that answered your question.
Yeah. And 'cause I think there was some maybe a little bit of confusion maybe around ASCO on the control arm, and maybe there was some pushback there. Can you just talk to the interest level you're seeing despite some of that maybe pushback?
Yeah. So first of all, in the front line, and I was not that long ago I was treating patients like this, the standard of care, for example, in Europe, many centers are giving anti-PD-1 monotherapy. So pembrolizumab for them and these patients is actually okay.
Mm-hmm.
It's what they do. In fact, the EMA only approved Rela+Nivo if you're PD-L1 low, and they actually made a statement they wish they would have done that for Ipi+Nivo.
Mm-hmm.
If you look at the data, there's no benefit to add Ipi or Rela, relatlimab over nivolumab, which I'm going to call nivolumab, pembrolizumab, basically the same drug.
Mm-hmm.
And so it's not that hard already for many in those countries to make that determination. In addition, if you think about patients going into this trial, means that they want TIL, their doctors want them to get TIL.
Mm-hmm.
The idea is that they will, 50% chance, get TIL, plus they're getting pembrolizumab, which is the backbone of every major immunotherapy. Then, if they're on pembro and they fail, these patients who wanted TIL, didn't get it, can get it then. We are already pulling in patients who really want the promise of your best shot on goal is your first shot on goal. When you see data like this, a CR of 30%, and you compare that to CheckMate-067, for example, at the same time point, which led to their label being in single digits. You look at other trials that are similar to ours, where CRs led to almost ubiquitous ten-year survival without cancer.
That kind of promise is very, very exciting to patients because we no longer live in an era where people want two, three-year survival, and mPFSs, mDORs, they're talking decades.
Mm-hmm.
Talk to me about decades, and really, what else is there out there? In fact, we're just about to get ten-year data on CheckMate-067 coming up. We already have decades kind of data for TIL. So I think there is definitely a population interested. The approval for AMTAGVI is added to that interest, and I think another accelerator will be when some more data comes out from TILVANCE-301. So I think there's a growing interest, there's no question. And then lastly, and I don't want to belabor this, is that there are some centers that want to cut their teeth on TIL. Coming into a very easy population to work with, where Iovance is kid gloving them through the process, is a very nice way to start yourself off on the trajectory to ultimately be an ATC.
Great. And the TILVANCE-301 study has a dual primary endpoint of ORR and PFS with an interim analysis of ORR. Why do an interim ORR analysis, and could you get that approved on an ORR analysis?
That's really a big deal, actually. The FDA wanted this trial, and we did a lot of negotiation with them. The beauty of this is, you know, ORR is a big deal, especially when most... half of your ORR are CRs. I mean, it's not a typical ORR.
Mm-hmm.
Still, that being said, what the FDA has told us is that if our ORR reads out, which we hope and think it should, that would be enough to, number one, move AMTAGVI second-line into full approval, which is a big deal, because now, as a full approval, that would have to be the control arm of anybody else coming in. Secondly, though, the ORR is enough to make TILVANCE-301's frontline an accelerated approval.
Hmm.
And then the secondary endpoint of OS, which takes longer, would be what we would then need to make full approval for frontline. So it's very helpful if this really is that much better. Patients are going to want to know that right away, and so be able to read out early is great for patients. And in addition, anybody who's on, for whatever reason, hedging their bets because it's an accelerated approval, will only add more confidence to it to be a full approval. So that ORR accomplishes many things for us, our patients, and the physicians we work with.
Fantastic. Let's touch on lung cancer as well. You know, you're taking a similar regulatory path in lung cancer as you took in melanoma. So you have the ongoing LUN-202 study, expect to reach full enrollment next year, top line data in 2025. Kind of recap what the interim data from that LUN-202 study have shown.
Yeah, so two things to note. One is, before I address that, you know, we had a short, historically short clinical hold. In fact, we were taken off hold the same day we sent in our responses. But still, when you turn the oven off, it takes time to turn the oven back on. And I bring that up because we were planning on it likely of having had data this year, and that's sort of why we're not giving more data. I think what's exciting about LUN-202 is that we didn't just see an overall response rate, which we put out in our press release last year of 26%. We saw that we did not reach duration of response, which again, is the strength of TIL therapy. It's that long durability.
Over 70% of patients that we could evaluate had responses that were greater than six months. So these are really exciting areas for a field that knows many of the patients fail frontline therapy, and there's really nothing else out there. And yet here we have a therapy that's following a similar playbook as melanoma, that not only can yield results in patients that have heretofore nothing, but also have durability, which we don't know what that durability really is. It could be, you know, the sky's the limit in durability.
Mm-hmm. And so help us set expectations then for the data in 2025. You know, what would be considered a positive result? What do you need to show on ORR and DOR?
Yeah, so I think if we continue to have in the twenties in ORR rate, we're doing very well because it's still way beyond what's out there. And then if you look at the, like, mPFS is four months of what we're, you know, comparing against. The bar is sort of low for durability, but I do think that we're, you know, we would like to see continued extended durability that we're seeing. I don't know if we'll stay with not reached, but I am expecting a pretty, I mean... much, much better durability than what's available now to patients.
Great. And any nuances that you see in the lung cancer market versus your initial experience in the melanoma market so far?
I think the big issue is that one, of course, there's 15 times the number of deaths in the United States alone for non-small cell lung cancer. That's a big difference in terms of unmet need. The frontline therapies, which are helpful, are not as helpful in lung as they are in melanoma, but also the health of the patients. We talked earlier about melanoma and the window of opportunity. So lung, it's a big deal. You know, the lung patients, a lot of them have had surgery in the lung, they've got lung metastasis, they may have had radiation to the lung.
One of the things that we did do in our trial is to allow the PI to, you know, reduce the dose of lymphodepletion, which is really where a lot of that challenges come. I think being able to identify the right patient is a little bit more rigorous in the lung cancer world, but there's so many more patients in terms of actual demand, it'll still way outpace melanoma.
Great. And maybe squeezing in a quick one on endometrial and a newer study for you guys. Kinda why has that been added to the priority list for TIL?
Well, it's the same playbook in a way. If you think about it, looking for a solid tumor where there's surgery involved, where there's immunotherapy, backbone frontline therapy, right? And there's no second-line therapy. Look around, where you know, how many of those are out there? Well, endometrial pops right up. And, you know, we don't have the mechanism of action for endometrial, but we've seen MOA for our other cancers, and it seems that TIL doesn't depend on some of the MOAs that the PD-1s do. So if you fail PD-1, you don't wanna just sort of give something similar, you wanna give a game-changing therapy. So we're hopeful that TIL will do the same thing that we've seen, for example, in lung cancer, where the PD-1s can't work, and sometimes you would predict them not to work, and the TIL still worked.
If we can see something similar in endometrial, in a way, it's like the lung is one step behind melanoma, endometrial is one step behind lung. We hope to follow that same playbook into the same success we've seen in melanoma.
Great. How broad do you think you can continue to expand that strategy?
I'm gonna let Jean-Marc talk from a financial standpoint. That's probably the biggest barrier because there's a lot of excitement in TIL. People want us to see in other indications. I'll just make one quip, and that is, my group runs the investigator-initiated trials, and we do, you know, put our feelers out for different cancer types, and the interest in other cancers has never been greater than it is today.
Mm-hmm.
But I don't know if Jean-Marc-
No, it's like we have to be mindful, but he's right. I think, you know, going through IST is the right path, and I think we have enough now.
Mm-hmm.
And then there's the next generations of technology, of course.
Mm-hmm.
We talked about the pivotal registrational studies in frontline melanoma, lung, endometrial is next. Then we have the first genetically modified TIL, PD-1 inactivated TIL, which we refer to as IOV-4001. That's completed the safety lead-in phase, and now it's in a multicenter phase II. So that's the next one. Then IOV-3001, the IL-2 analog, should be entering the clinic shortly. And then we recently announced IOV-5001, which is IL-12 tethered TIL.
Mm
Which is in preclinical development. We have high hopes for it, for potentially improving efficacy further in additional indications. So it's both a new technology and potentially looking at additional solid tumors.
Fantastic. So yeah, lots of exciting pipeline updates in the next coming months here. So maybe just in the last minute, I'll turn it back to you guys. Just kinda end us with kind of why investors should be paying attention to Iovance over these next twelve months.
So first and foremost, I would say AMTAGVI. AMTAGVI has the potential to address more than 20,000 patients annually with advanced pretreated melanoma. We've filed in Europe, so look forward to European potential approval next year. We're planning to file in the U.K. and Canada this year. Again, this should come to fruition next year. Australia, filing next year. And then the pipeline, we talked a lot about the pipeline, and next year should be exciting from this standpoint as well.
All right. Well, fantastic. Well, I think that was a great summary, and with that, we're out of time. So thank you for being with us.
Thank you for inviting us.
Thank you.
Thank you.