Barclays as one of their biotech analysts, and just wanted to thank everyone to our Global Healthcare conference in Miami. It's perfect. Really pleased to have them up on stage with us. Management from Iovance. So we've got Igor Bilinsky, Chief Operating Officer, and Brian Gastman, EVP of Medical Affairs. I guess the first question, just with the initial launch, and we got some initial metrics at least around how things were proceeding. If there's any feedback you can share around how launch is progressing over the last few weeks, that'd be great.
Thanks, Peter. Good to be here. Good morning, everyone. The launch is going very well, exceeding our expectations. We started day one at launch with an unprecedented number of authorized treatment centers, about 30 for a cell therapy launch. The first patient underwent tumor procurement the first business day after approval, and then commercial manufacturing of Amtagvi started the next day.
Yeah, I think it's really pleasing to us to be part of a historic launch, not just because of the first-in-class, but also the number of ATCs being the largest that we believe in cell therapy history. And what we're seeing is a very strong, robust interest from those centers that obviously have invested to be part of this momentous occasion.
Perfect. Thank you. Just in terms of access, reimbursement, what's the feedback been like so far from reimbursement organizations and decisions?
Yeah, so we've seen significant alignment with payers. A lot of that was done prior to our launch. I know our head of commercial has said multiple times how we were able to establish a DRG 18, whereas a lot of cell therapy companies had to start with a 16. I think it's also important to note that the IPPS system is exempt at certain high-level cancer centers. Most of those are aligned with our or part of our ATC. And so what you see between those Medicare/Medicaid exempt centers plus the rest of the centers, we expect that grouping of patients to be about 75% of our cohort. And so overall, though, we're quite pleased with our alignment with payers.
Gotcha. And then is there a bolus of patients in any way, or how do we think about that as kind of the patients that were ready and waiting, and how long does that go on for?
So the term bolus or wave, if you think about it as the shape of a mountain, I think we're just the beginning of going up that mountain. What we saw are a lot of centers that had already identified patients. And at this point, we could say the majority of centers have identified at least one patient. We publicly announced some of our early numbers. Since then, those numbers have matured, and we're pleasantly seeing the evolution going in the right direction. And so I would say at this point, the larger, maybe less nimble centers are just really starting to get their stride.
So I expect this just to be the beginning of the wave or the bolus or the mountain, the initial one. And so we expect this just to continue. I should also add that the centers have told us, and we expect that with experience, they're only going to want to do this more because it's going to be something simpler for them to do than the first patient they're trying it on.
Peter, you may have seen there was an article published in Precision Oncology maybe a week or two ago, and one of the KOLs, actually from Florida, from Orlando Health, mentioned that they have about 13 or 14 patients at their center who are waiting for Amtagvi and going through financial clearance. So that's one example of a number that's quite high.
Gotcha. Would you regard that as kind of a log fold out or a standard deviation out of the normal, or is that normal?
Well, yeah. We don't want to give guidance, but there's a range, obviously. Some ATCs are large, and you'll see a lot of patients. And one, for example, already had 2 surgeries on a single day for 2 different patients with tumor procurements. But there's quite a range. Like what Brian mentioned, the bolus then gets spread as more and more ATCs come online, we're getting bolus from those. So essentially, we're expecting to see a steady ramp in the number of patients over the months.
You kind of view this more as it's a steady ramp, or there's some kind of initial flow of patients that don't repeat, in a sense?
Well, from each ATC, there's a bolus of patients who've been waiting for some time, but then additional new patients come in. And I don't know, I'll use my math terms. If you integrate a bunch of delta functions, you get something smooth because different sites come up at different times.
Perfect. That's a great way of explaining it. You could also add the fact that our ATCs represent a mixture of pretty much all high-functioning cancer centers of different sizes. Some of the smaller ones are more nimble, and so they came on very fast. Some of the bigger ones, which have actually discussed publicly how many patients they're going to have, I think another one in Florida said they expect at least 60 patients a year just from one center.
A lot of them wanted to wait until we actually got approved before starting to discuss with patients. They're a little bit more of juggernauts, but once they get going, they're even much bigger. I think that gives us a lot of enthusiasm that the bolus is going to just continue, or the wave is going to continue to get higher, and as Igor said, even wider, perhaps, as well.
How should we think about, like I said, revenue starting 2Q? Is that kind of an end of 2Q thing, or beginning? How do we think about the timing of patients in taking sample, etc., and growing stuff up and back?
Peter, we're not giving revenue guidance yet. As you know, the first patient underwent tumor procurement soon after approval, so we expect revenue to start picking up early in Q2.
Okay. Thank you. And then how does that get reported out? Do you have the IL-2 and TIL reported out separately, or?
Again, we'll share that once we report the first quarter of revenues. Please stay tuned. Just as a reminder, each patient receives Amtagvi, and then they typically receive about 18 vials of Proleukin to help with T-cell proliferation. Those would be rough numbers. Again, please stay tuned for the first quarter of sales, and then we'll share that information.
Okay. But it's something internally you can easily track, right?
Oh, easily.
Whether we get to see that level of granularity of IL-2 versus TIL.
Absolutely.
Okay. Perfect. I guess a question that always comes up around manufacturing with ATCs has been difficult in some instances. Just how do you look at failure rates for your own product?
So in part, we built our own manufacturing facility to control our testing, so to speak. The OOS rates, again, too early to give guidance. But in general, the trajectory we expect to see is similar to other cell therapies where initially the rate may be a little higher, and then it comes down on the second half of the year after launch as the patient profile changes to earlier lines of therapy. And so we expect to see that type of schematics, but in specific numbers, let's wait until we get the first quarter of sales.
Gotcha. Is there a difference in manufacturing success for early-in-line patients versus late-in-line patients?
What's different is maybe Brian, you can speak to that.
Well, yeah, there's a lot of advantages for the commercial setting over what we saw in the trial. So first of all, the trial, the average patient had between 3 and 4 lines of previous therapy. And you can imagine the type of patient who has gone through 3, 4, even 9 lines of therapy, what's available surgically to resect and make the therapy because remember, the surgery is the foundation of what we use. It's our building block, so to speak, for our manufacturing. Also, patient health and dropout, a lot of that was because these very sick patients, they were going on a clinical trial. Your physicians can make changes very quickly to what is now the first approved drug for melanoma in the second line. Every drug that's used in the second line, it's not in their USPI except for Amtagvi.
So we know from onboarding our ATCs and the KOLs that are there that they plan on making real-world decisions, not clinical trial-based decisions, which are much faster. All of those will allow us to get earlier patients, healthier patients. And in addition, this concept of bridging therapy, which immediately excludes you from your trials, is now allowed in the real world. So there's a lot of reason why because you talk about out-of-spec, it's also dropout. The dropout rate certainly should be lower. We have a lot of interaction with this peer-to-peer process to reduce poor patient selection or increase good patient selection.
And also to discuss with them framing of our drug with the patient's actual biology of disease. And then finally, tumor selection. A lot of times, what you'll see is in these earlier-line patients, and I say this as a clinician who just came out of 18 years of practice, they generally have a lot more options surgically than a lot of these six-line patients who've had radiation and other various therapies, intra-tumor therapies, etc. All that together gives a significant advantage for the commercials in terms of Amtagvi over what we had to deal with with Proleukin. Yet that was enough for us to get FDA approval.
Gotcha. Thank you. And then I guess one more question, we move on, but COGS. What would that look like eventually, and where is that at the moment?
Generally, we expect COGS to be similar to CAR-T, but we don't need to deal with lentivirus. Again, without getting specific numbers, the trajectory, we expect COGS to improve over time as always with medication, specifically with cell therapies. As you go down the experience curve, and as you go down the scale curve, the COGS gets better. As we get higher volumes, better capacity utilization, and as we introduce additional improvements in the manufacturing process that are intended to cost of goods that our team's working on actively right now.
Gotcha.
I think it should be noted also that the COGS for Proleukin, which is this percentage of the whole therapy, is pretty well worked out. And Igor probably could tell you more than I can, but that's already fairly optimized already.
Okay. Perfect. Thank you. I'd love to move on to TILVANCE study. Kind of what you started in 2Q last year, how's involvement proceeding for that?
It definitely meets the definition of a launch underway. We've activated sites both in the United States and around the world, Canada, Europe, Australia, and other countries. You can imagine with Amtagvi, there's renewed interest in patients seeking out the therapy in various time points in their cancer journey. Overall, we can say that it is well underway, which is exactly what the FDA expected from us as part of a validation study.
Gotcha. Thank you. And then the expectation for that trial in terms of response rate, PFS, etc., does it have to beat Ipi/Nivo, Rela/Nivo? How do you view that?
Well, so first of all, the trial was designed with two endpoints, which has a strong advantage. For accelerated approval, we only need one of them. So ORR reads out much quicker than the other endpoint PFS. So in terms of when we will see it, it could be much quicker than multi, multi-year studies. Secondly, when you compare our data that we had, which the signal allowed us to even consider this, which was our 1A data, we had a 67% overall response rate at 25% CR rate. CR rates are actually quite low, even with Ipi/Nivo, Rela/Nivo. But that is very favorable. It gets both of their ORRs. And so I think we match quite well in that setting.
Okay. Perfect. And I guess I'd love to touch upon just the kind of very quickly, at least before we I'd love to jump back to the lungs, but just pivot for cervical to endometrial cancer. I know that's happened over the last six months or so. Just kind of if you walk through the kind of the logic there and why make that pivot.
Well, I can tell you why endometrial. The company's philosophy is really to hit an unmet need in solid tumors, especially common epithelial cancers. If you look at endometrial carcinoma, like the other ones that we are actively pursuing, such as what we did with melanoma, there really isn't a good second-line option for those patients. It is a cancer that is your therapy is used in the front line. Sounds a lot like a melanoma story and a lung story. And so it was very intuitive that we would go after that.
And because we had worked with gynecologic oncologists in the cervical world, we had a lot of inroads already built into the system to move forward with an endometrial cancer. The KOLs were set. They already knew us. We knew them. And so it made a lot of sense. Whereas in the cervical world, it continues to evolve, and we will obviously, at some point, we'll report our data there as well. But right now, I think there's a major unmet need for endometrial cancer, and that exactly aligns with our philosophy.
Gotcha. And I guess when do we see data? What's the bar? And kind of, yeah, those are the two main questions there.
Well, the bar, sadly, is sort of low because there really isn't a good second-line therapy for those patients. Chemotherapy in the second line is poor DOR and really poor ORR. So there's ADCs in that space. There are other companies trying to find something, but the last major conference was ESMO. And if you saw the endometrial data there, it's pretty clear that there's a large opening for different therapy.
Perfect. Thank you. And then just back to lung, if we think about you've got complete enrollment for the phase II, in sort of 2025 for the LUN- 202 study. Just if you want to talk through kind of the importance of that trial and kind of when we should expect to see data.
Well, I think the first thing to note is we all know that trial's on hold. However, in almost historic expedition or speediness, we were taken off a hold. We broke every expectation that I had heard. I wouldn't say instantaneously, but basically, the FDA knows that we know how to assess concerns that they have. And we clearly hit the mark right away because we essentially accepted all of our provisions, and we were taken off hold extremely quickly once we took the time to address their concerns.
And so the issue with once you're on hold, though, you have to go back to those sites, and you got to do the addendums, and those addendums have to go through the IRB. And so each site has its own timeline for that. So obviously, our timeline, which was faster before the hold, is going to be delayed somewhat. Still, we are quite confident that we'll be able to meet the timelines that we had publicly.
Gotcha. How has that changed, whether it's the inclusion, exclusion criteria, as you came off hold, adjusted in any way?
So we publicly haven't gone through all the protocol details. What I can say is even before the hold, we were already assessing reduced lymphodepletion regimens, which was well accepted by the physicians to care for these patients because they both have to deal with any complications from the cyclo, but also have to deal with the potentiality of changing efficacy. And the people who actually treat the patients, it's really important to listen to them, and they felt very comfortable with the options we gave them.
And all I can tell you is that what we addressed with the FDA, in part, is aligned with that philosophy and absolutely is in line with what our KOLs, our PIs, and our trial want us to continue to do. And I think basically, we're just trying to make it a safer trial. Obviously, it wasn't that far off because we got off hold very quickly, but also maintain the efficacy. And we think with what we've proposed, we can do both.
Gotcha. What gives you the confidence around kind of maintaining the efficacy as you've changed the conditioning?
Well, if you think about just what we do as a company and in medicine, we usually go from known to unknown. So the known was 60/25 of cyclophosphamide, Steve Rosenberg. That was in our LN-144 trial, right? But the typical melanoma patient has never seen hematopoietic-suppressing chemotherapy. Thus, their hematopoietic reserve is much better than a patient who's a second-line lung who's been through a significant round of chemotherapy.
So likely, they don't necessarily need as much lymphodepletion to get the same kind of effect that we need to see. Remember, lymphodepletion has many benefits for TIL therapy. And there's data out there that's not just from us but from others that we can get what we need out of a lower-dose cyclo, but also the fact that our physicians who've already started working with us prior to the hold have also clearly discussed that with us that this should not change much from an efficacy standpoint.
Gotcha. Okay. I'm just going to jump in the last seconds of this, just jump back to the TILVANCE study and just PD-1 usage in the neoadjuvant setting. Is that allowed, and does that change the potential outcome?
We do allow for it in the trial. However, we expect it to be a very small number for a number of patients, which I could go into, but I can just say quickly, it should be a very small percentage of our trial.
That's kind of low 20% or lower than that?
I expect it to be lower, much lower. But I can't give you exact numbers.
Perfect. Thank you so much. It was a pleasure to chat. Thank you.
Thank you, Peter. Thanks, everyone.