We're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies, and it's my pleasure to have the iAdvance team with me. To my direct left is Coraline Roche, CFO, and to her left is, for our vote, Interim CEO, President, and General Counsel. Welcome, both of you. Thanks. Thanks for having us. So for investors, briefly, who are less familiar with the story or revisiting the story, can you please give us an overview about Iovance, what you're doing at the company, what programs you have, and then milestones over the next six to 12 months would be very helpful.
Sure. Iovance is, we believe, is the largest independent cell therapy company in the world right now. We're fast becoming a juggernaut across all aspects of cell therapy from the earliest stage next generation assets all the way through to the commercial assets right now. We manufacture and produce TIL therapies, tumor infiltrating lymphocyte therapies. We've got a very large commercial launch underway right now with our product called Amtagvi. It's one of the key pillars of our organization right now. That launch is going really well, accelerating very rapidly, including in the community with treatment centers that are coming on board frequently this year. As you go back in our pipeline, we have all sorts of interesting catalysts and additional indications, ranging from non-small cell lung cancer. And Andrea asked about stuff in the next six months. I think you'll see more from us in the next six months on non-small cell, which we can talk about more as we go here. All the way through to early phase assets, including the first IL-12 tethered tilt therapy now that we just announced recently was cleared by the FDA to enter the clinic. We've got registrational programs underway now on two sarcomas. based on data we announced this year and we've got what could be a registrational program going in serious endometrial carcinoma based on data we announced just a few weeks ago at earnings so I'm sure we'll get into all the details as we go here but we're we're kind of the big leader in this
space across all aspects of it great um thank you and so to start high level and tag the it's growing nicely sounds like Q2 will rebound nicely but big picture second-line melanoma remind us the total addressable market to help us frame what kind of peak sales this drug could have ultimately yeah globally in
melanoma we should be able to reach more than 30,000 patients in the markets that we think are the ideal markets for cell therapy in the US alone we expect peak sales to reach over 1 billion from Amtag V and ProLukin combined at some point over the next couple of years as we develop and grow. So it's a relatively large market. And we have the non-small cell lung cancer market, which is about seven times that, and many other
markets besides that. Okay. So there's plenty of penetration, or room, for peak sales to grow.
Plenty of room for us to go. Obviously this year we guided to 350 to 370 right now. We're aiming to beat that. We'll talk more about that I'm sure today. But that's just, you're talking about two
years into the launch right now great thanks for setting that framework and so as for the launch itself you know big picture also is just conceptually as we think about 2026 2027 the key drivers behind the launch to get it to accelerate even faster maybe talk about your key priorities for increased
adoption yeah right now we have some some really key drivers and I know you're gonna touch on real-world data at some point here but the evidence that we have out there, both from our original clinical trial that got us approved as well as real-world evidence, paints a very compelling picture for AmtagV as the product of choice in the second-line setting. Response rates as high as 52 percent, and I know I'll probably ask about this, but at ASCO we showed some data, and we've been showing a lot of data that strongly suggests that about half of those patients are functionally cured of their cancer. So it's a very successful therapy. It works really well. It's a driver for growth and commercialization because we can communicate all that with prescribers and with payers and with patients. We are driving very hard right now towards 110 or more than 110 ATCs, what we call authorized treatment centers, in the United States and a few outside the United States right now. A lot of those, and we'll probably talk more about this at second quarter earnings, are community centers, meaning large community oncology practices in the United States where the bulk of patients right now are being seen. And that part of our launch is really accelerating. But the academic medical centers, which is sort of the backbone of the initial part of the launch, are doing very well, too. Quite a few of them are continuing to grow, and we're still onboarding some of the large academic medical centers.
Okay, great to hear.
So those are really the drivers of the launch.
Yep, and so you mentioned ASCO. Yeah, it would be nice to kind of dig in a little bit more. Long-term survivorship, it sounded as if 50% of the patients in clinical studies are functionally cured after 10 years, and it sounds as if their mortality rate is in line with a normal patient. Is that kind of one of the takeaways, and maybe share more details about that?
Yeah, the poster at ASCO, and there's other data we've put out before, including the five-year overall survival data from 14401, our main registrational study, all suggest that when you get a deep response to AMTAGV, you're not going to relapse. And this is actually consistent with the original data from the National Institutes of Health, Steve Rosenberg's data, where he saw the same thing. He had a number that sticks in my head. If the patient was in response, there was a 96% chance that patient would not recur 10 years later in one of his papers that he published a few years ago. So we're seeing the same results with our teletherapy, and that's what we showed at ASCO in that PIVC you mentioned.
And you're taking this data as well as the clinical data to educate the community to treat earlier because treating earlier does matter.
Absolutely. The real-world data that we put out at ASTCT, a conference in February this year, shows that when you treat in the second line, you get a 52% response rate. When you treat in the third line, it falls to 33%. So the second line is on label. We can treat it second line as we show them, and that data has been very useful with prescribers and with patients.
And so as we think about the launch so far in Q1, most recently, typically or historically, you've had this kind of manufacturing period. It's fairly short, but it does impact your sales and perhaps margins, and I think that's somewhat of what we saw in Q1. But the question is, going forward, though, can we expect anything like that, or have you kind of fixed this kind of dynamic?
So the short answer is no, don't expect that going forward, because we now have all of our manufacturing in-house with the ability to have continuous supply. And we achieved that through the upgrades in Q1. And, yes, there was a little bit of – let me take it in two parts. A little bit of impact TAMTAGVY revenue, about $5 million. It was down $5 million to $60 million in Q1. The revenue did absorb the period of time that we needed for the upgrades, but that is the last time we need to do that.
Great. And so looking ahead, I think during the Q1 earnings call, you mentioned how coming out of that maintenance period, maybe April, the uptake, the patient uptake was looking the strongest ever for that month. And so I'm curious, May, June, how's that looking? Is the momentum sustaining as we think about Q2?
Just to remind you, we did guide product revenue for Q2. MTAGV was $79 to $81 million, so a big move from Q1 of $60 million. Why are we so sure about that? A couple things. The demand signal is really strong, and we had our strongest revenue month in March. I know you can't see that because you're just looking at Q1. However, that gives us good, I guess, a good ability to forecast Q2. Also, we have visibility into the quarter. So when we gave that guidance, think about we know what patients are enrolled, what patients have resections, and when they're planned for manufacturing for those batches.
And visibility, to be clear, because it takes a little bit of time for payer access and then the manufacturing turnaround time, maybe a month. That's how you have it?
That's how we have the visibility.
Okay. And so as we think about your four-year guidance, looks like 350 to 370. So if I added your Q1, Q2 sales with your Q2 guidance together, it's about $158. And so that means maybe $200 million implied for a second half of this year at the midpoint. And so do you have line of sight into that ramp, that second half ramp?
Yeah, so based on what we know, we feel very comfortable with that guidance. And that's why we guided the range that we did. And I think we're also pushing wherever we can to do more.
And is there room then to potentially beat and raise as the quarters come by or is this kind of fairly accurate type of guide? Or I don't know how to use the right word.
Potentially. I'll keep you posted.
Okay. Sounds good. And so as we think about revenues, then margins as well, and they've been steadily improving on a quarterly basis. Of course, Q1 is kind of an exception this time, but again, it won't happen again. But come Q2, I'm curious, Q2 and TAGV sales should be the strongest ever, it feels like. So compare that to Q4 margin. I forget, maybe your Q4 gross margin was 50%. Should we expect Q2 gross margins to look even better compared to Q4 is the question.
So I'm not guiding the margin, but I will tell you that the Q1 margin had a one-time non-recurring impact. so expect to think about it in terms of Q4 okay and then in terms of conceptually
though as sales grow on a quarterly quarterly basis by year-end if we should get better margins outer years we should get even better margins where that's the goal that's for sure the goal yeah and what remind us what kind of margins you've got it to that peak well we haven't got it specifically to margin
But we want to get to the level of about 70% long-term because that's pretty standard in the industry for a company of this nature And we think that's doable based on we know today about how we can improve efficiencies in manufacturing scale Volume this kind of thing owning our own facility is a huge part of that And having it be a relatively large footprint shutting down the CMO and getting some of the
The lower margin stuff out of there. Okay, very good. And you know as you scale you've done a good job curbing expenses along the way? I think you reduced OpEx to about $100 million a quarter now. Is there more room for improvement, more cost cutting, or are we kind of at the floor at this
juncture? I would say there's room for efficiencies. I mean, we'll have to invest here and there as we grow, but we're keeping it under control with very strong financial discipline. Okay. And so as we
think about expansion opportunities I actually lose track of your ex-US progress so can can you please remind me which where you are on the regulatory side of things which countries are approved ex-US and I think you just had
approval. We just announced something yesterday on that last aftermarket yesterday so yeah we just had an approval we announced last night aftermarket in Australia the Therapeutics Goods Administration approved AMTAGV. Australia's obviously has the highest incidence rate of melanoma in the western markets, so we're really excited about that market long term. We're going to have an ATC up and running there relatively soon for private pay patients, and we'll enter, and we are entered, into the reimbursement process, which, as I'm sure you know, outside the U.S. takes a while, so it could take some time to negotiate. We want to make sure that we have consistent pricing approaches in other countries, too, because we've got the U.K. pending right now. We've got Switzerland pending as well we also have Canada already approved same deal there and we will probably talk a little bit more about additional markets soon and some of the other things that we're planning in that area from melanoma other high-incense markets Western markets that we think can work or countries where you see a lot of medical tourism or patient concentration into
particular metro areas I see so in those certain regions it would be your intention to market independently at the structure yeah we may partner with
distributors in certain areas but we would not partner in any kind of significant way on a JV type structure we would we'd be only in the distribution agreement with minimal financial impact us okay and so bigger
picture again sales are growing nicely and it is kind of a high unmet need for this indication there are technically competitors in the horizon potentially and so maybe speak to your differentiation first and foremost and why you think mtagvi is unaffected should there be increased competition
well I don't think there's gonna be any near-term competition for mtagvi in the first place meaning in the next couple years there's there's a competitor out there that's got multiple CRLs and is attempting again to get approval based on some data that they showed at ASCO, which it's difficult for us to understand why that would affect, why that would alter the FDA's thinking for them. They showed some OS data, which is not something FDA considers an accelerated approval, and they also showed that their median duration of response fell dramatically, which is something FDA does consider an accelerated approval for single-arm studies, so I just don't know exactly how that's going to work out, but you've heard me many times probably at one these conferences before i i talked about this and you know you can go read the crl and it pretty much matches what i was saying back then uh there's another competitor in the till space it's really very very far behind us many many years doesn't have the scale the manufacturing capacity it's hard for people sitting in a room like this to understand but ivans has enormous scale and an enormous mode around it's intangible and tangible property to make this stuff we are the leaders in this space. It's very hard to catch up with this level of capital investment that's in here, and now we're really looking to drive that forwards and leverage that out and make sure we get some successful returns for investors.
Right. And as we think about your indication expansion opportunities, out of curiosity, you have your own center. How many doses can you supply each year, out of curiosity?
At least 5,000 patients a year, and I wouldn't be surprised if you hear us take that number up quite a bit as we continue to work on efficiencies.
And so sticking with melanoma, second, now you're doing in the pipeline, there's a first-line melanoma study, the TILVAN study. You're trying to move upstream, ultimately, in that study. And so can you remind us, I think the study actually has a dual purpose. So can you just remind us the latest and greatest on the regulatory side of things, what you have agreement on with the FDA?
Yeah, first let me just say that the reason we run that study is because an oncology is a general rule. you want to put your most effective therapies first with patients so we have a I just mentioned earlier the real-world data shows a 52% response rate and second-line patients with am tag be we have Steve Rosenberg's data in the frontline population before checkpoints were even approved that shows 56% I think was a response rate back then no checkpoint alone including pembrolizumab gets that level 33% versus 50 so really that the therapy of choice should really be frontline, and that's what Tovan's 301 is designed to do, is put it in the frontline. Now that study is set up to both confirm the benefit of the accelerated approval, which we already have in the United States, as well as obtain another accelerated approval in the frontline and a confirmatory full of traditional approval in the frontline. So it does three for the price of one. It does that through an interim analysis. I don't know how much detail you want to get into here, but basically there's an interim analysis that will allow us to confirm the benefit in the second line and get the accelerated approval on the front line and then it reads out finally to confirm the front line.
And for the second line confirmatory, is it PFS or OSS or ORR, I mean, that gets you?
For the interim analysis, it's going to be ORR to get you accelerated approval on the front line and PFS to confirm the benefit in the second line. And then when you read again later at the end of the study for PFS, that confirms the front line. There's no OS end point. There's a secondary OS, but OS is not a regulatory primary end point, which is actually really important. We have crossover in the study, too, which would be confounding on that. Jeff Dea allowed us to do it.
And so you just mentioned PD-1 in first line mono. It sounds like they do 30% OR, give or take.
Yep, that's what's on the label.
That's the bar to beat kind of thing.
Yeah, we have that study I should have mentioned. That study we're running in combination with pembrolizumab versus pembrolizumab. yeah so contribution of elements is sorted out by that but it also puts us in combination with the preferred single agent in the frontline setting right now and we think that study will perform better than if you Nevo does in the frontline setting which is the current really the really the bar if you want to think about from commercial regulatory bars yes Pembro yeah but it be
Nevo is the the commercial bar we have to beat that understood and so how's enrollment go this is a 670 patient study how's enrollment going any color
when we might get the interim not yet it's going well there's it's only 600 patients in the main analysis set 70 patients are adjuvant patients we're exploring them as well but it's running it's at a lot of centers we had a lot of excitement about it at ASCO we had an investigators meeting in the middle of ASCO that I attended myself and was was really thrilled to hear some of the stories of how fast patients were responding and how deep they were responding. It's really, in the words of one of our investigators, it's an extraordinarily powerful therapy in the front-line setting for these patients. And like I said earlier, if you put a patient with CR very quickly in a couple of weeks, the odds are 10 years from now
very good that that patient will still be like that. Okay, exciting. And so moving on to second line lung now in a pivotal phase to also going after the accelerated approval approach. but here actually it's an open label study but I think what is what is the hurdle I guess or the regulatory pathway what do you need to show in this upcoming update in second half 2026 to be able to file and get an approval I think you've guided an accelerated approval maybe second half of 2027 yeah
yeah so we're we're nearly obviously you can from those timelines estimate that We're nearly complete on enrollment right now, which is true. That's where we are. The regulatory bar for this is, well, the regulatory decision for an accelerated approval is going to be based on ORR supported by median DOR and DOR. And as you know, we put out data already showing the ORR was 26%. This is just within the last six months we put this data out. And median DOR was not reached with 25 months of follow-up. So it's looking good for this patient population right now. And I think we'll see in the final analysis what it looks like. We have to do an IRC read, but if it continues to hold up at that level, that should be enough for us to get approval in the second-line non-small-so-long setting.
And when you share the data later this year, do you intend to press release first and then share it at a medical conference? What is the kind of disclosure strategy?
We've got to figure that out, but it's probably going to be a press release followed by a medical, because just the timing of these things, the medical conferences don't line up well with some of the things we want to do as a company. but we very we're very devoted to getting stuff out of medical conferences so you can see the full data set and we always play that game so stay tuned and
we'll see what happens sure but bottom line is you're close to completing the enrollment target of around is it 80 patients yeah roughly okay so that it will be a sizable readout because off of memory the last cut was about 39 patients? Yeah, it'll be about double that. Okay. Okay. And so is there a strategy for now to go
first line also in lung? There could be. We will have to have a confirmatory study, and so we'll talk about that probably around the same time that we put the data out to tell you what our strategy is, because that's obviously something we must be talking with the FDA around around the same time. It's possible to be in front line. It's possible to be in second line. It's possible to both. Obviously we think that TILs work best in the frontline setting but with an indication as large as lung you can really enroll very quickly into a second-line study and if you're gonna go head-to-head with docetaxel with something that has a higher ORR and clearly a much better MDOR you think you probably would win on PFS so you may run that study it might be faster and easier. We'll figure out we're working on that hard right now. Great and and so I
I guess relatively recently there have been FDA changes at CBER with a B, and so by chance have you spoken to the FDA recently to reconfirm you have an accelerated approval pathway for a second line, for instance?
We have, and we think we do, and we're in constant contact with the FDA. The management changes there are really not affecting the day-to-day review team and the teams we meet with when we have our type BCD meetings and that kind of if those kind of exchanges we were just recently got fast-tracked for long and I think that helped confirm a lot of the analysis that we were doing and you can just assume it's true we are in constant contact with them we're constantly having meetings on one thing or another and yes we feel pretty comfortable that
nothing's changed on that front okay good to hear and so then shifting to some of your other programs cancer programs I think endometrial you had some initial phase two data or is it was it earlier this year but anyway can you
share it's just a few weeks ago in May put out the it's all a blur we have a 40 percent response rate and a small initial number of patients in serious endometrial which is the most deadly histological subtype of endometrial cancer and then we also have data we put out three months prior to that and two sarcomas UPS which is undifferentiated pleomorphic sarcoma and D-differentiated liposarcoma or DDLPS. Both of those showed very high response rates, 50% response rates. That's an indication that it doesn't have checkpoint approved in the frontline, and we can really go post-chemo and really do some good there, because you're not selecting off the patients that are the good IO responders by giving them checkpoint. Now we'll get them all coming through. And so those are both, all three of them are both, I don't know how you say it, all three of them are good shots at getting additional approvals in the very near future on single-arm trials so
this is like for instance the endometrial program where you showed data the current study is it designed as a pivotal type so you just need a crew more patients kind of correct correct okay any color how many patients you need and is 30% quote-unquote enough and satisfactory for FDA 40% but yeah yeah
I think that would be more than enough for FDA with some good durability which we'll have to generate. Typically for these single-arm trials for accelerated approvals in oncology, you're seeing about 80 patients. 80, you said? 80, and yeah, we have a lot of approvals, especially for biomarker or smaller populations like UPS and DDLPS, as well as serious endometrial. There's been a number of approvals over the last two years coming up through the summer where people have gotten on about 80 patients, and so we anticipate probably something similar. But in each one of those cases, we're talking and the FDA getting that feedback, making sure we make those adjustments right away.
Okay, and then the two rare sarcoma studies where you saw 50 to 55% OR, I mean, you mentioned there's no PD-1, just chemo, so it feels like the bar is a little bit lower. Is that fair to say?
The bar is low in all of them if it's, you know, there's nothing available for any of these lines, but yes, when you're dealing with UPS and DLPS, you're looking at chemo most of the time anthracycline in the frontline setting which has lower response rates and very poor durability in many cases so we'll be will be coming in behind that for the accelerated approval and then we could
always try to move up into the frontline setting okay and any color when we might
get more data cuts not yet but there's a lot of conferences at the end of the year where sarcoma is a good option to present so just stay tuned on that front Okay. Clearly we want to get the data out soon so you can see the full scope of it.
Sure. And how big are these indications? They're substantial size. So you put all
three of them together, you're larger than melanoma. You put UPS and DDLPS together, it's about seventy-some percent of melanoma, we think. Okay. A couple thousand patients a year
at each one of them. Sizable. Okay. And so maybe finally then, well, unless you have more in the pipeline that you wanted to mention, but I did want to ask about this new, I think it was like an IL-12 tethered program.
Yeah, yeah, we just announced that.
Can you maybe describe what that is with a differentiation? I'd be keen to understand more.
IL-12 is a cytokine that's been in everybody's mind for the last 40 years. It's one of the most powerful cytokines to potentially achieve an anti-cancer response. It's a very pro-inflammatory cytokine. The problem with it has been how to control it. When given systemically, it causes toxicities, when given through different injection approaches or through devices and stuff like that, there's been all sorts of complications. At the NCI in 2015, Steve Rosenberg published his work on an IL-12 secreting till, and he had, with very low cell doses, about 100 to 10 fold lower than what we give today, he had a 63% objective response rate in those patients. And in particular, we saw patients, he had a patient who we personally know, actually, who received regular TIL therapy, lithium tag V, relapsed, and then was given IL-12 tethered TIL or IL-12 secreting TIL therapy at a dose that was about 100-fold less than what she got in the initial thing, and she went into a 10-year response. When we have a longitudinal patient like that, you kind of know there's something hot there. So both Steve Rosenberg and I and the teams have been looking at this for years. Steve had developed the tethered technology. We licensed all this at NCI a few years ago, and now we're taking this concept with some additional bells and whistles on it that we've added to it into the clinic. We think it has the potential to turn immunologically cold tumors hot, and that's why you see us targeting things like colorectal, triple negative, any AR low breast, and more. So it really could expand the platform to hundreds of thousands of patients, and this is something you can't do with a bispecific. You can't do it with a T-cell engager there's nothing else out there for these patients that works like this so if this works it could
truly be the game changer that's why we're so excited about it i see so that's starting uh phase
one or two phase one safety but it will roll directly in the phase two okay very good basket that's got a modular ind so we've got we've got the ability to add indications but we've already
got a whole number of them in there okay and then um anything else you wanted to mention from the
pipeline i know you're working on a lot yeah we have two other good assets uh 4001 which is our PD-1 knockout, and we could be putting data on that out soon, too. That's another one that's, I think, up for discussion with investors so they can see what we're cooking there. And then we've got 3001, which is our IL-2 analog that abrogates some of the side effects of IL-2, of proleukin, which we own, the product that we use today, but without giving up some of the efficacy and the T-cell growth factor performance that we want to have. So that's also in safety right now and is in dose escalation, and we could have an update on that, too, when we talk about some of that data.
And then maybe finally, Coraline, cash position, and then how should we think about, I mean, from here do you have enough cash to see everything through as you're scaling, for instance, and potentially turn profitable and maybe talk about the cash.
So our last disclosure regarding cash was about $320 million at the end of Q1. We've said that we're expecting that to fund operations into 2028. However, how are we going to go further than that? And I am obviously doing this every day. I'm looking at when we can be profitable. So increase revenue, increase margins, and control spend. That's the main goal. And I think we can get there.
Thank you very much for the updates. I appreciate it. And thank you, everyone, for listening.