Okay, great. I think we should get started. Thank you. Thanks to everyone for being here. My name is Yanan Zhu. I'm one of the biotech analysts here. So today, we are fortunate to have Iovance Biotherapeutics management team with us for this fireside chat. With me on the stage is Chief Business Officer, Howard Johnson, filling in for Fred, CEO Fred. And we also have Brian Gastman with us. He is EVP, Medical Affairs. Great, thank you for being here.
Thank you.
The company's tumor-infiltrating lymphocyte therapy, Amtagvi, was approved by FDA mid-February for the treatment of post-PD-1 melanoma. And the commercial launch has been closely followed by investors. Could you walk us through the launch dynamics so far? How has it evolved since approval, and where do you stand now? Where's the launch headed in the next few months?
Sure. Thank you, Yanan. Pleasure to be here. So overall, I would say, our perception is it's going quite well. A lot of the dynamics are driven by the authorized treatment centers, aka ATC. You'll hear that term a lot. We started out with 30 authorized treatment centers when we launched in February, and as we had told this, the street, we would have 50 by the end of May, which we did. We currently have 51 authorized treatment centers, and this gives you a sense of the growing demand. In fact, the plan at this point is to have 70 by the end of the year.
I think these type of high-level institutions, which really partners with us, shows the commitment that they have and why we thought we could do this in the first place. Overall, I can tell you that month over month, the demand continues to grow, that we are meeting the capacity of that growth, and we foresee this to continue. We have no reason for the foreseeable future to not see this just continue to be to improve and expand positively.
Got it. Thank you, Brian. So now that we are one month into third quarter 2024, are you, compared with your earnings update, are you feeling confident about the third quarter revenue guidance of $53 million-$55 million you announced at the time of earnings? Is there a potential for upside surprise?
Yanan, you referenced obviously we gave guidance on our second quarter call for third quarter, fourth quarter, and 2025 revenues. And the answer is, we're very confident in that revenue guidance. We wouldn't have offered it unless we were very confident. And the reason that we're confident is because of the reasons that Brian just gave for why the launch so far has been very successful. We have a growing base of authorized treatment centers across the United States. Each of those centers, as they come online, they start slowly because of financial access being put into place because they're setting up their own infrastructures, right, to be able to treat one to multiple patients each month at each center. So we're seeing that.
We're seeing that, in the early stages of the launch, the first two quarters of the launch, and going into the third quarter. We're very comfortable with our revenue projections because we see the demand out there. The other piece of this is, of course, capacity to meet the demand, and as Brian said, we are investing, very strategically, very thoughtfully, but we're investing in the demand that we see to make sure that we have manufacturing capability, for the patients, that are coming into the system.
If I can just add one more point. A lot of this is driven by the fact that we were early on approved to be within the NCCN guidelines with the best category we could get, which was 2 A. That really helped loosen up the payers to consider getting a policy in place so that we could speed these processes up. Currently, the vast majority of patients are now covered in the United States, and we soon hope to have the whole country approved. But really, that kind of start helped us to accelerate the process. And ultimately, since the payer side of it, in terms of pre-approval and authorization, is a large time sink, that's gonna actually contract significantly as part of this acceleration, accelerating process.
Got it. Maybe digging into more about the launch dynamics in detail, what are you hearing from centers that have infused patients? What's the level of satisfaction on the overall operation, logistics, and product turnaround time? Are there any sticking points for improvement?
Yeah. We've been very pleased by the partnership and collaboration we've had with our authorized treatment centers. What we've seen is that a lot of them had to learn the process. So for a cell therapist, which is part of the trifecta of the cell therapist, surgical oncologist, and medical oncologist, this is old hat. This is the seventh launch. But for the other two, it's their first launch. And so a lot of them had to learn about flexibility, that, you know, if you only operate on Monday, then we have to—you, you're only gonna get slots on Tuesdays, or if you do lymphodepletions on certain days, we can only harmonize with you so far. And as they've gained flexibility and understand why they need to, we've only seen a greater trust and greater efficiency.
I think for that reason, what we're mainly experiencing is a very positive effect from those centers. As a result, because we know that there really isn't a challenge that we aren't overcoming, we don't really see many logistical snafus and sticking points, which is great because it's dynamically always becoming more efficient, and we do active learning to constantly put back into the system to make it better literally week after week.
Got it. Got it. Are there, if I may ask, centers that are underperforming? If so, is there anything that you can do to support those centers?
Well, first of all, I can't call any center underperforming. We have some centers I'd say maybe are. I don't want to say overperforming, but are maybe doing better than we expected at this time, time point. We do know that some centers are very methodical, but we also know that some of the most methodical, slow to start, will be the most busy in the future. That's part and parcel of why they are, they're such complex juggernauts of systems. But what's unique to Iovance, and I take a lot of, I'm very happy with my team that was able to produce what we call the peer-to-peer and the medical affairs response team.
These are unique groups within Iovance, which you really don't see in any other company, that takes previous healthcare providers, like myself, and have active communication with healthcare providers, making treatment decisions, even inside the operating room while a surgery is going on. Literally asking someone like myself, who used to be a surgeon, or someone, you know, others who have been nurse practitioners on the cell therapy ward, "What would you do here? What are your thoughts?" We can't prescribe, we can't tell them what to do, but we certainly can work with them to impart literally minute-by-minute information, and that's a way we really strongly support every system, and so a lot of them are fledgling. This might be new to their system, or maybe parts of the system it's new to.
We really help make up for that, so that there's no one that should be underperforming. I would say there are just some that are more methodical and more and want to take a little bit longer than others, but what we can see is some of the ones that took the longest time to really think out the process are now really performing extremely well, and it's very exciting to watch that process undergo.
Got it. But to the extent you can comment, you know, I think you had 55+ infusions since launch as of the earnings update, right? So, so are there clusters of high-performing centers that are accounting for a significant portion of those 55+ infusions, or do you think it's more, or, you know, how more evenly distributed in that regard?
So we knew going into this process that the six previous cell therapies companies found that 50% of all CAR T was done in top 10 centers, and 80% was done in their top 40 centers. We expect something similar. May not be exactly the same because melanoma is a different dynamic, the trifecta of the different doctors I discussed is a different dynamic, but we're starting to see some of that fall into place. There will be top centers and then sort of medium centers and so on. There's also the issue of some centers have incredibly enthusiastic KOLs, and they went out of the gate running as fast as they could.
Whether they will stay in the front and other bigger centers that didn't need to be as enthusiastic because they have a lot of things going on, catch up or even pass them, that we may still end up seeing. But overall, we are seeing trends towards a similar distribution. And one of the reasons why we have so many centers opening is because we wanna make sure we find those best, best-in-class 40. And, we don't know who the 40 will be, so having 70 by the end of the year should help us ensure that we get the best coverage. Because ultimately, it's not just about the number of cases, it's also about patient access.
We don't want patients to have to travel multiple states to get Amtagvi, and we're already achieving that. I think the average patient does not have to travel more than 200 mi. The goal is to get that even smaller, and that really depends on which region of the country you live in.
Got it. In 2025, do you still look to onboard additional ones beyond the 70+ , or do you think you reached a good size by now?
I don't know if we made official decisions, certainly, to say it publicly. I will tell you, many centers beyond the 70 are constantly contacting us. It's hard to say no to all of them. So, you know, I can't- I think if they push hard enough, and we have a need, we will do what's appropriate. But ultimately, patient access is probably the greatest measure driver of why we make our decisions.
Okay, great. Thanks for all the color regarding the centers. If we may dig into patient journey a little bit here. How long is the current enrollment to infusion time? What are the components of this time?
So generally, publicly, we say around 8 weeks- 10 weeks from ordering to actual infusion. We have seen that contracted even further. The components, which can be done in parallel, they don't all have to be done in series, includes the ordering of it, which usually means that you've done a tumor board type analysis of the patient. You know, really well-vetted physicians who we've done training with to become part of the authorized treatment centers, have deemed this patient an on-label, appropriate patient for Amtagvi. From there, things have to occur in terms of getting authorization, which is speeding up tremendously with the amount of payer coverage that we now have that we didn't have when we launched, obviously. Two is then you have to schedule a surgery, and that surgery is harmonized with a slot.
The more flexible the centers are, the more capacity they will find themselves being offered. We also have programs where we white-glove service these centers as well. Sometimes if a slot isn't available, we can, our team of case managers can move things around and really do magic, and it's really amazing to watch them do this, to get the centers what they need. Initially, a date might be X, but then we can cut that in half through different activities, and they are gaining a strong confidence in us that we're able to do that. Once a slot is assigned, usually the day before is the surgical date. If the slot is a Tuesday, usually they're operating on Monday. The surgery occurs, which is a surgery. It's not a biopsy.
The surgery can occur anywhere in the body, that there's a tumor volume that's appropriate. That tumor is put into a special solution, into a bottle that we provide for them, that gets shipped to our centers of manufacturing in Philadelphia, and in a 22-day process, which is the same for every single patient, we produce the product. From there, as you can imagine, if you're a patient, you want to have quality assessment and assurance, which the FDA also required. Currently, the total additional process adds to around 34 days of what we call turnaround time. So you have surgery here, 34 days, we're shipping it back. And if all goes well, which it almost always does, we harmonize with that center's lymphodepletion, which is the pre-TIL preparatory phase, and then they immediately get the TIL, and there's a very short, you know.
That interval can be really minimized by that harmonization. And so, that's the ordering to vein, so to speak, which is 8 weeks-10 weeks. We are starting to see that come down to 6 weeks-8 weeks. We hope to get that shorter and shorter and shorter, and eventually there are things in the system like working on the manufacturing side and the quality assessment side that we are already looking into to constantly make that shorter. I should add also that every day that we can shorten on our end, sometimes that can add to one or even two weeks of earlier infusion because of the timing of lymphodepletion, which happens to be in the hospital that week.
It really can make a huge difference, and we are actually looking at centers to try to identify opportunities like that to really speed this process up, patient by patient, constantly trying to do better.
Very, very helpful. Thank you for going into such details. Maybe just, maybe there's one point in that chain of events that is scheduling of the manufacturing slot. Can you talk about how well can you accommodate requests, and what is the average wait time?
Sure.
Why don't I-
Yeah, go ahead.
I can take that, Brian. Yeah. So yeah, to answer that, Yanan, I think it's useful just to understand, you know, the commitment and the investment that, that Iovance has made in, in manufacturing. Autologous cell therapy manufacturing is at the heart of it, right? Because every patient gets their own product made for them, right? As and as Brian just walked you through, there's, there's a patient journey, that. The first step in terms of the manufacturing journey is really scheduling a manufacturing slot. We think, we think very carefully about the capacity that we have, and capacity is a very important treatment involved in the treatment decision, but it's also involved in the financials of running a cell therapy company, right?
If you need to have enough capacity to meet demand, but you don't want to have too much capacity that you can't fill the slots, right? So we think very, very carefully and spend a lot of time about the right capacity, seeing the demand on the horizon. What is the right capacity that we need to build for today? Right now, our facility is built for 2,000 patients in Philadelphia. We have our own facility that we've invested in, and we're built for 2,000 patients. We have a CDMO across the street that can also handle an additional bolus of patients as well. We are hiring right now. If you go to our website, you will see posted job postings for manufacturing technicians, for quality assurance technicians.
We are hiring now because we see the demand on the horizon, that we gave guidance around, right? And so one of the first things we want to do is make sure that we remove the friction in slot scheduling. We want to have, as Brian mentioned, we want the authorized treatment center to be able to look into the slot scheduler and to minimize the friction of getting a patient's manufacturing slot signed up. We have special programs, white glove programs, where we, again, move slots around to accommodate, you know, situations that need to be accommodated in the short term.
But really, it's our objective, right, to say, when you get that financial approval, right, that the patient has got the financial access to the therapy. You want to be able to manufacture, have a manufacturing slot available not too long thereafter.
Got it. I guess, is there a wait time, average wait time or, you know, could you talk about that or?
Really, the objective, again, is to minimize that friction, right? So, and what we do is, in advance of demand, we build capacity in advance of demand. And you see that in our numbers, right? You see that in the Iovance, in the Iovance reporting. And so that's really the objective, and we're doing that in advance of, obviously, what we see as a growing revenue curve, not only in the next two quarters, but going into 2025 .
Right. Right. Thank you. Thanks, Howard, for those insights. Can we talk about manufacturing success rate, as well as patient dropout rate, if you can make any comment of your experience so far?
Sure, I'll take the first crack, Brian, and you can also weigh in. You know, it's in the early stages of the launch. I would say our manufacturing success rate is good. We're not seeing anything different in the commercial setting that we didn't experience in the clinical setting. So I would say, you know, we acknowledge that, you know, that there are patient dropouts, of course. We acknowledge that there is out-of-spec product events that happen, but we have programs to improve both of those metrics, and we believe that this is the early stages of a cell therapy launch, and this is gonna improve over time, and we're working and focused on it.
Yeah, just to add, in terms of, you know, patient dropout for non-manufacturing reasons, there is a lot of education that we're responsible for to give to the sites, and we learn all the time ourselves. Generally speaking, good in, good out. We want good patients who are found in their window of opportunity. The vast, vast majority of Stage IV melanoma patients should be good candidates for Amtagvi, the vast majority, and maybe I'll say the vast, vast majority. Where we lose some of them is if someone doesn't take the window of opportunity when it should have been taken. Some of that has to be educated even at the level of the community.
In fact, we have a community initiative, but even beyond our ability to get to the community, the NCCN guidelines, for example, is developed for community physicians, not for quaternary, you know, Ivy League-type hospitals. It's really meant to educate those type of doctors what to do because they don't treat melanoma every day like the, you know, the University of X type places. And they, the other side of it is the ATCs, the authorized treatment center themselves, are putting into place, both through media activities, but also just getting out there, to try to re-educate what is a true second-line patient. Because in the past, second line meant hospice, palliation, recycling therapies that didn't work, but just cobbling them together. And so once they do that, we're gonna see even improved levels of what you call the dropout rate.
And it's already happening, but I can tell you that the good news was we did do a lot of education before we launched, and so we minimized that problem to begin with. But as Howard said, this is early days. I can't quantify any of that to you. All I can tell you is that the best part of my job is the partnership I have with the physicians treating these patients and how open-minded they are to these concepts, and it's just every day is better than the day before.
Got it. Thank you. Thank you. So, let's talk about your longer-term guidance numbers. So you had, at your earnings time, you put out 2024, 2025 sales guidance, which reflected your confidence in the launch. Those are very strong numbers. So, you know, just one question might be given the amount of data you have, because you haven't, you know, the launch happened mid-February, right? Do you have enough data points that you feel you're confident to project the sales numbers with, you know, that far out? Can you talk about your process here?
We do. We wouldn't have offered the guidance, again, if we didn't have, you know, great confidence in being able to meet it and hopefully exceed it. We have a deep understanding of each of our ATCs. As Brian mentioned, the relationship, the peer-to-peer relationship and also the relationship on every level of the ATC, the business relationship, the logistics relationship, is a very intense and close and informative relationship. So we know across each ATC as they come online, you know, how many patients they're gonna treat early on in their cycle and what their potential is, as they get more established, as they get their systems in place, as the financial access issues are resolved. We know what their potential is.
And we also know what our capacity is because we are investing in that capacity as we speak, in anticipation of seeing that demand. So all of that adds up to the confidence that we had, not only to give guidance for the next two quarters, but also into 2025 , for the four quarters of 2025 . The demand is there, the capacity is being built to meet that demand, and therefore we have confidence in the revenue numbers for 2025 as well.
Got it. Got it. And you know, the guidance number includes both Amtagvi, the cell therapy, but also Proleukin, the IL-2 component of it?
Correct.
So, you know, we don't have granularity of, you know, what's the sales number for Amtagvi, but you did say Proleukin should, at steady state, should only account for 15% of the overall number. So I was wondering, how long do you think you could reach steady state for Proleukin? Are we talking about a couple of quarters, a little more than that, or could it be longer?
Yeah, so I think as we continue to add authorized treatment centers, right, you're gonna get closer to steady state, right? So I would say give it a couple more quarters, going into 2025 , and eventually those ratios, right, the Amtagvi to Proleukin revenue ratio, will hit a steady state. But as you have stocking, right, if you have stocking of distributors, if you have stocking at sites, right in the early days of a launch, you don't see steady state, right? Yet, right. But it's gonna come, and it's gonna come as we level out on adding additional ATCs in a more measured way.
Got it. Got it. So lastly, you know, just, looking into the guidance number for 2025, you guided for $450 million-$475 million. I guess a very rough, kind of estimate based on the, the, the WAC of, the Amtagvi price is roughly probably 700+ patients, is what you might treat in 2025. Are you confident in handling that many patients? You know, as you said, you need capacity that should be able to accommodate scheduling fairly easily, although you don't want waste capacity, right?
Correct.
So probably capacity shouldn't be exactly at 700 , but more than that. Do you feel comfortable that you have the capacity to achieve, deliver that guidance?
We do. I mean, again, capacity is at, and manufacturing is at the heart of an autologous cell therapy company. We spend a tremendous amount of time, thinking about it and making sure that, you know, we have that right balance, right, between supply and demand. And, we, feel confident that, that we can give you projections because we know that implies a certain number of patients will need to be infused next year, with Amtagvi. We know what that means in terms of having a manufacturing facility and a CDMO ready to make the product for those patients, and, we know that, that those two, that balance is gonna be correct, right? And so as a result, you have your guidance.
Okay, great. Thank you. Maybe a question on the EU front. You submitted your filing in June. When do you expect EMA to validate the filing? When might be the EU approval timeline, and how big is the ex-US opportunity compared with the US opportunity?
Yeah, in the dollar value sense, we see the rest of the world opportunity being equal to the U.S., right? There's more patients, you know, less product cost per patient, price per patient, but there's more patients outside of the U.S. So the dollar values are approximately the same in terms of U.S. and rest of world opportunity. The E.U.- I always think about this as accelerants that we're putting in place for revenue, and one of those is ex-U.S. filings, right? And we started with the E.U. We also have the U.K. coming up, Canada, Australia, and all of those will be coming online in the approvals in 2025 and 2026 . Again, you know, on being accelerants to our revenue curve, right?
Adding additional demand, adding additional revenue to the Iovance story, and we're building the capacity now to handle that demand. One of the points I wanted to make is that the current facility is built for 2,000 patients, but we have made the commitment now to expand what we have as shelf space to create additional clean rooms so that the facility in Philadelphia will be able to handle 5,000 patients per year, and that's because we see these accelerants of demand coming online outside of the U.S., as well as in the U.S., as well, because the projection for next year, the guidance for next year is all U.S. guidance.
Right. Got it. Thank you. Maybe we can touch on TILVANCE-301, the pivotal frontline study. How is the enrollment going, and when can we expect an interim readout of the ORR endpoint?
So in terms of enrollment, you know, we've always said it's well underway. I would double down on that, it is definitely well underway. We already have 40 centers up and running in 10 countries. We have another 60 centers that we're vetting, which would be a total of 18 countries. It's really an international Phase III trial. We do expect to keep our timelines. We have not publicly said when we are going to report data, but it is a dual primary, and it has dual endpoints. Overall Response Rate, ORR, will allow us to report it earlier, potentially even to go back to the FDA earlier. Really, it depends on, you know, how well the arms separate, and how many events occur. So we're sort of, you know, waiting for that to occur.
That being said, we're very confident in how this trial is running, and we're seeing, I mean, more sites approaching us, more sites are opening, and so we should only see this continue to grow. So I can tell you, right now, it's a positive activity in the company.
Got it . Maybe one last question on that. I don't know if you can comment on what is the bar for success on ORR endpoint?
Of course, we know in the frontline what the different checkpoint inhibitors. I think what we are looking for is something similar to our 3A data. We presented this year at ASCO frontline data. That trial was started because of incredible results that were already presented at the NCI with TIL therapy, where they had a complete response rate of 25%, and 96% of those patients were alive at 10 years. Nobody's reported 10-year data in a major trial yet. In our 3A data, which is much more like our TILVANCE, modernized by the addition of the PD-1, which is also in TILVANCE, we showed a complete response rate of 30%. So it was even higher, with up to that interim results, excellent durability. And so we are looking for something along those lines.
Keep in mind that the checkpoint inhibitors like ipi/ nivo and nivo itself, in the similar timeframe cutoff, had single-digit complete response rates, and we're presenting 30%. And we don't know, you know, as time goes on, will our complete response rate even continue to go up, as did other checkpoints, as did our result in LN-144? So I think, you know, in some ways, we could tell you an overall response rate bar, but I think the CR is a new bar that we are creating ourselves, and we're trying to look for something similar to what we saw in our 3A presentation.
Great. Thank you for those insights. Lastly, I wanted to touch on non-small cell lung cancer. So you're developing TIL in second-line setting in a pivotal trial ongoing now called LUN-202. I was just, you know, curious about the goal that you want to achieve. Second-line lung cancer has many, many drug development activities going on. Everything has demonstrated not so great ORR, PFS. Median PFS is also pretty low, as you know, looking across the landscape. What do you think TIL can bring to the table, and what is the bar for success for the lung LUN-202 study?
So first of all, it's important to understand the unmet need is even bigger in non-small cell lung cancer than it is in melanoma. 150, depending on the numbers, even 108,000 deaths a year in the United States alone. It's a very big problem. And yes, there's a lot of activity there, but you're seeing a lot of that drop off with multiple negative studies out there. The current, you know, docetaxel or other, you know, combinations that are used are really almost palliative. They have very short duration of response. So what we bring to the table is an overall response rate in hopefully maintaining it in the 20s, but more importantly, is those responses having extremely long durations of response.
We don't even know how long those might end up being. Those could be, you know, we hope they never end, of course. That kind of promise is something that's completely missing in the field. In addition, what we're also seeing is that a lot of companies are focusing on the same patients, PD-L1 high patients that have failed immunotherapy or in that space. Our mechanism of action, we've shown, is unique and distinct.
Probably why we see the duration of responses that we do, but also allowing us to crack those nuts that other companies can't, because we're agnostic to PD-L1 status, for example, in our responses. I think there's a lot to offer, but the bottom line is this unmet need, that the patient population is desperate for something that will give them long-term outcomes. TIL today, to me, is the only thing out there that has been reported to offer that.
Got it. Got it. That's... Yeah.
I mean, at a high level, I mean, you know, we have been successful with the playbook of LN-144. Around 120 patient trial, single arm, because there's really no good comparator. The FDA has been very lockstep with us on that. That's how bad the second line is, and so we want to do something quite similar. And ultimately, as we get to that level, you'll also see a similar TILVANCE-like trial in lung. But again, there's such a huge need, and there's a need even in the frontline. But of course, you gotta bide your time, do one thing first. So that's, those are the expectations, those are the kind of bars we're looking at.
Got it. And the LUN-202 trial, we can expect data 2025 , is that still-
We haven't given an exact date. That's what we're hoping for. Keep in mind that we had historically short, but still an actual pause last year. It was short because the day we gave them our response, they unpaused us. But we took our time to respond and, you know, I called it like turning off an oven. It takes time to turn that oven back on. But we're already seeing accrual starting again, it's already started again. Sites are all coming back online, and we have a very nice plan that's actually working to add really good sites.
And this is also the international trial, even beyond the U.S. and Europe. So I think you're gonna- w e hope to, as Howard would call it, have accelerance there as well and get this really going in a timely fashion. But I can't give you the exact date when we're going to report that yet.
Got it. Great. Great. I think we are out of time. Thank you, Howard, thank you, Brian, for a very informative session.