Afternoon, everyone. Thanks so much for joining us. I'm really pleased to be joined by Brian Gastman, EVP of Medical Affairs, and Dan Kirby, CCO of Iovance. Thank you both for joining us.
Thank you.
Dan, maybe I can start with you here. Just, you know, given AMTAGVI has been on the market now for over a year, what have been the biggest learnings from this launch? What has been maybe easier in some ways, or what has been more difficult than maybe the pre-launch expectations? Brian, I'll pull you in here since you have been here for the entirety of this launch to date.
It's a great question. I joined in February, and looking at the first year of launch for AMTAGVI, a lot of success was had following the CAR T launches. Really, the centers being so receptive to the first time that cell therapy was there for solid tumor and treating patients was a great experience. You saw that in the first year of launch. As we get to the learnings from the first year and where we go as we expand past that, it is really the identification of patients that can be referred in earlier in their treatment journey.
Looking at in metastatic melanoma, the number of patients and just the opportunity there to get to them really brings us to the point of going earlier with the patients into the community to be able to get a better capture of more patients early in their journey to be able to treat. That is really where our focus is in the second year. In short, great launch. The next wave will bring even better success for patients.
Yeah, I'll just say, add quickly that the enthusiasm as you see these ATCs mature has just increased. The number of feel-good stories of patients getting complete responses. We had nothing else as an option. We just hear about it all the time. Sometimes we hear about it on the news, but many times it's the centers themselves. That drives enthusiasm not just in their hospitals, but also internally in our company.
Maybe to that point about the feel-good stories, the evidence of AMTAGVI's benefit in patients. You did recently present at ASCO five-year data. Maybe speak to what you saw, what you presented, and just how meaningful is that for this patient population?
It's huge because, first of all, I like to call it rare air. There's never been a study in the post-PD-1 setting that's prospective, that was a registrational trial that has ever even come close to this. Remember, this is a one-time therapy. The overall survival was based on that therapy alone without salvage therapies to raise that number up. To be a five-year final analysis, that's like a seven-year interim analysis of a 10-year study. 20% of patients were alive at five years. A third of the responders were still at the five-year mark to be analyzed. This is huge because when you get these kinds of responses, you know you'll be able to treat your patients and be with them for years on end, maybe even decades.
I think for both the referring physicians as well as the authorized treatment centers themselves, this is a big shift for them to really think that this is something that's not just about responses, but about durabilities of those responses.
You guys hosted a panel. One of the things that I was struck by was one of the physicians talking about the meaningfulness of AMTAGVI and being able to essentially bring patients to a cure for nearly 60%. When you combine it, when you think about checkpoint inhibitors and then AMTAGVI following thereafter, a majority of patients being able to reach a cure. How much has that been appreciated by the broader prescribing community?
It is certainly growing. Number one, it started off that KOL panel with Dan Olson saying straight over two dozen patients with at least 40% response rate. One of his main referrers, Bruce Brockstein, is the one who mentioned that. This idea that the ideal sequence is you have your front line followed by AMTAGVI gives you those incredibly high numbers that you mentioned. I think doing anything other than that sequence in their minds is no longer standard. This is the right way to go. If that majority is not that person's journey, they still have the myriad of other options to choose from. I think as centers have these feel-good stories, as it gets out in the community, this message is getting stronger and it is getting louder.
One thing to state into that is from a cell therapy perspective at the ATCs, it's to be expected. They've had cell therapies starting with allotransplant 50 years ago. To give a one-time therapy and have a durable response, it's less surprising to them. When you get into the med-on community and the referrers, that's something that we have an educational opportunity because they haven't seen this before. When the patient's done literally after they're infused between the lymphodepletion to the actual finishing of the regimen, it's a couple of weeks and there's no need for ongoing treatment with it to see these types of responses. That's something that's been eye-opening in the community and something that we're working to continue to educate on.
Maybe one other point that one of the KOLs mentioned is that what they're seeing in the real-world setting is exceeding what your clinical trials would suggest on a response rate. Maybe how broadly applicable are many of your other physicians also seeing such high success rates? Maybe talk to us about what you're hearing from the ATCs.
I think it's key to note that in our LN-144 trial, the average patient had at least three prior lines of therapy. They really exhausted everything. Many of them had those same therapies doubled and triple compounded. What we're trying to educate the community is that this is a truly second-line therapy. As they move toward earlier intervention, not only does it cover the vast majority of all melanoma patients in the setting, but also gives these kinds of outcomes and maybe even better. Because we've had data in the front line setting, which had even higher response rates. I think the earlier you get to them is driving those numbers. The other thing that Dan Olson said as well is that he's treating patients that maybe traditionally we thought were harder to treat. We're resetting what is a hard-to-treat patient.
Altogether, you're seeing those kinds of numbers. We are hearing from other centers, not every center, but again, this is just word of mouth at this point. We're working toward with consortiums to get actual data to present. We're hearing numbers like this and even in some cases higher than that.
Fantastic. Maybe we can talk here about your 2025 guidance. Recently reset on your last earnings call. Just remind us what led to that revised guidance and then what gives you the conviction that the reset number now is truly achievable.
Great question with it. We did reset guidance between 250 and 300 on the last earnings call. What we did was we looked at the numbers of the patients coming in. And there is good and bad to the story with it. The good is the patients are there. The bad is they are not getting referred to the ATCs in time. We are seeing a lot of patients go to hospice or death as they go in. When we started looking at that and calculating out to 2025, we wanted to reset guidance with the plan of addressing the current ATCs and growth in the current ATC while we are going to onboard new ATCs within community networks. Again, we are looking at the speed to which to do that.
In 2025, that guidance is reflective of our current ATCs plus the new ones coming on and us driving referrals in there earlier from the community as we look for long-term. We're also simultaneously building out ATCs within community networks and different approaches there so we can bring the product closer to the patient.
What can Iovance do to your point to help drive that referring behavior, to try to ensure that patients really do experience the benefits of AMTAGVI versus unfortunately maybe being ineligible?
Absolutely. The first step is education. Right now we're working on a disease education campaign that's all about cell therapy. Because AMTAGVI is the only cell therapy for metastatic melanoma, we want to educate on cell therapy and one-time treatment with curative intent to the med oncs out there that would refer in. You educate them first. Secondly, we have a field for expanding that calls on the community. That is something that we're working now, giving them the messaging and having them go out. Again, as we get new ATCs up, putting them out in the community that are going to refer in and then having that push come in along with the education.
The third step here is really to talk to the leadership directly at community organizations and community networks and form a partnership with them to be able to not only have them refer in. In some cases, we have ATCs stood up in their area that they can refer into very easily, having that happen in the short term, but also aligning with them on which ATCs we need to stand up or hospitals inside of their networks that are already referral patterns existing that we can maximize. There are three things that we're doing right now to try to get that education and action out there.
You mentioned, you know, as you think about the number of infusions that you reported for the first quarter, 85 infusions, some of that being impacted by reduced capacity during the scheduled annual maintenance of iCTC. In that context of 85, you've then provided the guidance of 100-110 infusions in the second quarter. Maybe help us understand how much line of sight do you have to that, just given the timing of when you reported, when you made this, when you provided this guidance, how much line of sight, how much confidence do you have in that number?
First, we're very confident in that number as well as the number for the full year with it. Again, the full year is looking at 250-300. Now, when you look at the journey from a patient when they're referred in for AMTAGVI, they get referred into the center, they get enrolled. After they're enrolled, we schedule out a tissue procurement. We have the tissue procurement, and then we manufacture, and then it's delivered and they're infused with it. That is a bit of a time lag. We look at the leading indicators to say that we're confident that number can take place. Again, you don't know until the end of the quarter when the infusions actually take place that they're occurring with it. The modeling suggested that that's a viable path forward for it.
We want to make sure that we not only meet, but we want to exceed those numbers at the end of the year.
Got it. So the leading indicators all suggesting 100-110 is very much achievable.
We're confident in the number.
Great. Maybe touching on ATCs, I think as of your last disclosure, you noted 80 within your network. Where do these stand in terms of being operationally ready?
Most of them are operationally ready and treating patients right now with it. There are a few that have come on recently that are ramping up that journey. Typically, when an ATC comes on, they want to test a few patients out from an insurance perspective. Therefore, their finance department makes sure that it is going to get paid by the payer. They start quickening pace after that. There is also a learning curve on the surgeon side that Brian's teams work on to make sure the surgeons are getting a white glove service in the initial phase of it until they can get their legs under them, so to speak, and they know how to do the tissue procurement to give us the best starting sample possible with it. Most of them are up and treating right now. A few are coming on and ramping up.
We will continue to see that as we bring new on and then newer ones start evolving.
Are all the ATCs receiving this white glove treatment?
First of all, we certainly wanted to focus on centers that are new or older centers that have new surgeons. Mainly, we've always offered this option for every center. What we've done as a concerted effort is to actually go to the surgeons as well as pre-surgery tumor decision-making steps of the way and offer them anywhere from there to in the operating room and beyond to help them not only get the best tumor, the best preparation of the tumor, but also make sure that the patient gets to infusion and gets to that okay. What's happening now, though, is that because they're letting us in the operating room, when we are able to get in there, which is happening more and more, we're actually seeing a significant drop in dose-related out-of-spec, which is the most common reason for out-of-spec. We expect that to continue.
Also, as we say, we will let the birdie fly on their own because we do see once we've done enough of these and we've seen that they're able to do it on their own, they should be able to. It also should be somewhat infectious that surgeons should be able to train other surgeons for best practices.
How much of, to that point, once you're confident in their ability to do this procedure correctly, how much retraining needs to be done or over what frequency would you expect that you would need to maybe go back in, make sure things are still going kind of well there?
All of our teams, but we each do it a little bit differently. In my team in particular, we study each ATC individually and we track by time what's happening there, what happened each infusion, how much of the dose was in spec, whether it was in spec, out of spec, that type of thing. We have centers now that are doing so well. There really isn't much more we can teach them, so to speak. They're doing excellently. In fact, these are the kind of centers that we'd want to go out and teach other centers, like again, sort of infectious education. That being said, at that point, it's really just their communication with Dan's team and referrals and growth in the program. The goal is that everyone ends up being like that.
We have centers now that are really already in a sweet spot for that level of quality.
We also do, we look at the metrics all the time, as you can imagine, with every single ATC. We have quarterly scheduled business reviews with them where we go through and we tell them how they're doing, what their patient's response was, everything. We have those open discussions with them. If we see anything blip up, the teams are there right away to work with them and ensure it's corrected.
When you've reported some metrics as it relates to your ATCs, the proportion that have resected a tumor, have infused one-plus patients, have infused ten-plus patients, what does it really take to get an ATC from an infusion in one-plus patient to the ten-plus?
Actually, it's a lot of work in going on with them and making sure they have the right, mainly they have the surgery, cell therapy, and med onc, that triangle is working very well together. When we get somebody to the expert level of 10 plus, then it really is down to how many patients we can have referred in. Those are when we have the open discussions about who are the large community practices in your area and how can we help you network them. In some cases, we provide, in all cases, we offer, but some cases we join in with them on advertising that they do to those sites. I mentioned the staff that we can send into the sites.
Going through there and making sure that once they hit that expert level, we're sending as many patients to them as possible and putting the pipeline there so they can treat.
I guess right now, out of your 80 ATCs, what proportion are at that, remind us again, what proportion are at that expert level right now?
We're about 17% at the last earnings call we said, and that number continues to grow.
At steady state, any guesses as to where that number can go?
Steady state, as we look at not only with the academics, but as the community come on, over half of ours will be that expert going in where it's a relationship on they've mastered the TTP, the process with it, how to infuse, everything's going very smoothly with them. We anticipate over half will be at that level. The other half will just be ones that we'll work closer to to evolve them.
Got it. To the extent that you're able to share, but we heard from one of the KOLs, and you mentioned this, that they've treated double-digit number of patients right now. How many infusions have your top centers done?
Anywhere, I think the one that was mentioned was Dan said at 25. We have 25-plus in the top centers for it. We continue to see that number grow at those centers, plus also the new ones coming up. That is where we see them evolving to it.
When you've engaged with the ATCs and patient identification is such a key part of this process, to your point, what are they telling you with respect to the patients that are still available and still likely candidates for AMTAGVI?
We see new patient enrollments every single day and patients going through the channel as well as getting into infusion. There are a lot of patients out there. I think one of the things that we share with our existing ATCs is the urgency to get patients in there earlier because there is nothing more heartbreaking than getting the announcement. I have an email feed that happens every time an order or an enrollment is canceled. If I see patient deaths or hospice, I know that is happening before we can even get tissue from them. We have a joint effort with the ATCs to get patients earlier. That said, we get enrollments every day. We have TTPs every day. We have infusions every day. The patient numbers keep flowing through.
I guess maybe just remind us here, the profile of the patient that is receiving AMTAGVI right now. Obviously you want to move it to the second line. That is the ultimate goal here. What line setting are they predominantly right now?
Third line plus.
Okay. That hurdle, I guess maybe how much of a hurdle is it to get it to the second line? Is it just the education? It is the experience of these physicians. It is the earlier referrals. Anything else you can do to ensure that it becomes a more predominant part of the second line therapy?
I think the biggest thing other than what we talked about, and I've been talking a little bit about this, is the phenotype of the ATCs that we're going after and looking at where we're heading to the future with it and going where existing referral patterns are there versus trying to build them. That is something that the CAR T's talk about all the time, too. I think the famous quote they have is, "Two of ten patients receive treatment." I think we even have a bigger opportunity in metastatic melanoma by expanding the ATC definition.
As you think about maybe what you're seeing commercially and in the real-world setting relative to your clinical trial experience, maybe just put that into context for us, how similar or how different this has been as it relates to manufacturing or patient experience or the like.
It's been consistent on the manufacturing front. I do think that if you look at it from the real-world experience, we have the ability to treat more patients than clinical trials. That's something where we see those patients still going in and going through. On the other side of this commercially, there's so much more opportunity to get those patients in there. Again, we have a lot of later patients inside the clinical trial as well. Really going after that second line patient and going upstream is the huge opportunity.
So much of this really hinges on the ATCs, the quality of the ATCs and their level of familiarity, their expertise as it relates to this process. How do you think about bringing on a new ATC, just given the high bar that you need to be able to make sure that they're achieving? How do you think about bringing those on and what is the ideal number if it's not 80? If you're expanding, what is the ideal number?
One thing, I'll be consistent. I've never said the ideal number because I don't think it's a finite number out there. I will say we have changed our criteria. When we go to nominate an ATC, the teams have to establish with the ATC the referral patterns, what community presence they have, the fact that they have the ability to get patients from day one. That lift that I talked about for us is less on day one to get patients in and more about educating them on how to use. One instance that just happened recently, we said no to an ATC and they asked to be on the phone with me. They were listing out their criteria of clinic affiliations and everything. They were signing up for commitments for large numbers.
That was a great sign to see that the new process is working for it, that we can have them work with us and commit. We can see what their referral patterns are and the fact that they're an existing community network center versus an academic center that's relying on the community to refer in.
Just really reinforcing there the importance of the referral network that's really being leveraged to drive AMTAGVI utilization. I guess maybe as you think about the competitive landscape and how it's evolving here, particularly in the second line where you would ideally like AMTAGVI to be positioned, maybe speak to us about what you're seeing across that landscape and how you think that this might impact AMTAGVI.
I think with new competitors, the market always gives attention to metastatic melanoma and the need to treat for patients. I believe that during our panel at ASCO, this was brought up. The philosophy that Dan Olson and others said during the panel is the philosophy we keep hearing from the KOLs. When you look at AMTAGVI, it's a one-time treatment and you look at the long-term data now, what you want to do is you want to offer AMTAGVI first because that's the best chance for that patient to have a long-term response without having to be on chronic therapy for years or go through dosing cycles that can last four months and then two years of chronic therapy. If you look at the approach they have, it's really strategic.
If you give AMTAGVI first or evaluate for AMTAGVI first, you allow two shots on goal. You give the AMTAGVI. If you cannot give the AMTAGVI, you always have a fallback. If you can give the AMTAGVI, which is most cases, you proceed with that. You will know within a few months, with three weeks of start to finish, they are done their dosing. When they get a response, there is no need to go somewhere else. If for some reason they do not get a response, you always have that fallback that is sitting there for it. That is what we have heard. I think the noise is going to be helpful to the market with it, but also, we are confident with our KOLs that AMTAGVI is the first option.
Great. I guess maybe as we think about the regulatory path and the expansion into ex-U.S. territories, what learnings will you take from the U.S. launch to apply to the European countries?
It's a great question with them. We have our European and U.K. GM right now. Her and I talk about this about three times a week about what are the launches. Some of that is infrastructure and how we can approach better. That's one of the things that we can do internally to make sure we have a seamless between medical affairs, Brian's teams and my teams to ensure that we're working in sync. Also, to what we've learned in the community, I talked about going to where the patients are and asking them what centers to stand up. We have learned that of going to the government authorities and going to the centers and find out where the patients are right now from the derm ocs primarily in Europe and what centers we need to stand up on that side.
There is a straightforward selection process in some of the countries that we are going through right now to ensure that we can access those patients. It is within their infrastructure to do so.
Remind us here, you've noted how many ATCs you're planning on onboarding to support this launch in Europe?
15 ex-U.S . ATCs as we've committed to. We're well on our way to accomplishing that. We have over 10 deep in the process right now, halfway through the year.
What is the coverage, I guess, across those 15 ATCs? How many patients are associated with those ATCs?
It's hard to give you an exact patient number per ATC with it. What I can tell you is that there is a network mapping that we go through. In each country, it's a little bit different. I know the U.K., we're going through that right now of being able to select the ATCs there, but really making sure that they're within not only where the patient proximity is, but also to their centers that are authorized. Typically they're the cell therapy centers, but they have a good relationship with the dermocs, the surgeons, as well as the cell therapists.
It would be a fair assumption then for these ATCs, they are already familiar. They're interested in cell therapies and they're knowledgeable too.
We received a lot of interest proactively from ATCs outside of the U.S. in countries that we're pursuing.
How be your capacity to offer the white glove service to U.S. ATCs?
First of all, you should know that most of the ones that we are standing up outside the United States are ones that we are already working with on trials. Many of them have large experiences. They have very large infrastructures. Some of them, you might have seen them on panels already about cell therapy. These are the high-end experts to begin with. In terms of the white glove service, or I should say mirroring the services we have in the United States , we are actually pooling from a lot of our U.S. resources so that we do not have to completely double everything. In fact, you are going to see a much smaller footprint from, let's say, a medical affairs perspective to achieve the same thing we have there that we have here. A lot of our strategic leadership will stay here on this side because we have the experience.
A lot of things that we did less efficiently at the beginning will not occur, so to speak. The new centers will start at a much higher floor than the ones that started here. I think for all those reasons, there are things that will just be part of the norm that had to be changes or amendments in the United States that will just be something baked into the system. I think there will be higher efficiency, less of a need in general, and a smaller footprint. I do think we will be able to do the same thing there as we have here.
Any notable differences in the treatment paradigm in ex-U.S. territories versus U.S., or is it fairly similar?
I think it's interesting. One of the things that we were not seeing as an obstacle is what we talked about before, the community into the academic. It's much more seamless. Maybe it's a single payer structure. The financial incentives aren't there to keep the patient. Also, you have a much more defined treatment algorithm to be able to get them to the centers and evaluate it quicker. That said, we also need to ensure that the cell therapists and the derm docs that usually don't speak to each other are forming those relationships and going in. In fact, we've actually had centers. We've had the cell therapists sit through the onboarding discussion with the derm doc there and help the derm doc understand one-time cell therapy and how that is to treat their patients and how they need this. We've seen great responses doing that.
Great. Maybe one last question here on AMTAGVI, but as it relates to your frontline trial, just any updates you can share there? Particularly on the back of the ASCO data that you did have last year, what has been the receptivity to potentially moving AMTAGVI to the frontline setting?
TILVANCE , as we call it, is still on track. It's still our confirmatory trial. As you know, it's a phase III trial. A lot of it is happening in Europe to be consistent with what I just said before. That is also helping us sort of let these centers cut their teeth on the use of cell therapy through our processes. At a minimum, this is going to not only be confirmatory, but it's also going to promote good practices to try to get these patients as early as possible. At maximum, it would bring AMTAGVI into the frontline.
There is excitement for a therapy like AMTAGVI for the frontline.
When you see CR rates of 30%, and at least with Rosenberg's data, if you hit the CR, you have a 10-year, nearly 100% survival. It's hard to unsee that. Especially for those younger patients who are thinking about long lives with little children, this is really where this could have the most impact.
Great. Maybe just one more point here as you think about your revenue guidance of $250 million -$300 million. Obviously, a component of that is Proleukin. Proleukin generating revenue, not just from AMTAGVI, but a number of other sources. Help us think through how the Proleukin revenue cadence should look through the remainder of the year.
Absolutely. Great question. I know in Q4 we had wholesalers that were loading up. One coming on, the third major one came on. What we've seen so far this year is the bleeding down of that inventory with it. I had said in the last Zoom call we expected to reorder this quarter with it, continue that expectation with it, that two will place at least one order from us this quarter with it. As we look through the other channels with AMTAGVI, the manufacturing channel, you saw a strong purchase in the first quarter for that. We continue to put efforts against going to the other manufacturers for cell therapies and having them select Proleukin versus the other IL-2s. Proleukin is the only FDA approved for use in humans. There are reasons why you'd want to use that in your manufacturing.
We do have customers of ours that are other cell therapy companies with commercial products that are using Proleukin in their supply chain with it and having great success there. We do see that replicating across and putting efforts towards that. Of course, the clinical trial pathway for IL-2 use as well is a huge opportunity for us. We look at this. It's mainly going to be tied to AMTAGVI. Those other two channels are a pretty decent business to stand up on their own, and we're putting more efforts against that.
Great. Maybe in the last couple of minutes that we have here, just your pipeline, you will have two data reads coming later this year. Maybe talk us through both for lung cancer as well as endometrial cancer, just the expectations here.
Sure. So for lung cancer, we believe that we will have enough response as well as persistent durability that we've seen that'll be similar to the data that we've shown previously in previous press releases. That should be well within the metric that we need to be able to submit that to the FDA. Our plan is to have a large data set presented by the end of this year. We haven't stated specifically where we're going to do that. That's still under internal discussion. That being said, generally, those kind of large data sets tend to not change much as you add the last bits of data on patients so that you have the full registrational cohort to be able to submit. That's the main plan. The main thing is that since we started this, the landscape really has not improved.
It has actually been very dour, so to speak, because one would have expected some of these other therapies would have done something in that second line. The unmet need continues to grow, both for responses as well as durability of responses. In terms of endometrial, we expect to have a sort of signal-finding cohort by the end of this year as well that we are going to present. The key there is that we are looking at both proficient and deficient MMR patients. There is a need for both. The fact of the matter is that while lifileucel is an immunotherapy, its mechanism of action is distinct from checkpoint inhibitors. We have seen that in our lung cancer data. We expect to see that also here as well.
This is critical because, as you might see, a lot of immune-based therapies try to get those PD-L1 highs or very high hot tumors, so to speak. We do not necessarily need to fall into that. That gives us the opportunity not just to go into the second line, but also to affect patients where probably the first line was not that great either.
Great. As you think about lung cancer, I mean, you just mentioned second line, still very much an unmet need here. How would you anticipate a launch in lung cancer going relative to melanoma? I guess, are there parallels there? Is it more difficult? Is it easier in some ways?
I think the biggest thing, it'll be very difficult if we didn't have melanoma out first because what we've seen with lung cancer is very fast, and it's something where the patients are sitting in the community. Getting them to an academic center, a lot of times, even less so than melanoma, that they'll actually get there. As we look at what we're doing in melanoma, success we're having there, that is setting up lung very well because it's the same community treaters, and we will have already opened up those ATCs within the community network. That gives us an opportunity to launch fast and help as many patients as possible as quickly as possible.
Have you thought or maybe shared the expectations for what could this opportunity represent on a dollar basis? We've talked about melanoma. I think Fred has talked about this being a billion-plus opportunity in the U.S. alone. How does lung cancer compare to that?
It's multiples of melanoma. It really is. It's a huge opportunity going forward.
Exciting opportunity ahead then. Thank you guys both for joining us.
Thank you.
Thank you, everyone.