It's my pleasure to introduce Iovance, Jean-Marc Bellemin, CFO here. Thank you, Jean-Marc, for coming and joining us.
Thank you, Ren.
You know, I never know exactly who's in the audience, I don't know, you know, who might be listening to the webcast. So maybe just to-
Sure
... to level set, if you could spend, you know, two-five minutes telling us a little bit about Iovance and what you guys are about?
Sure. Thank you, once again, for inviting us to be here. So Iovance is the leading company developing and delivering cell therapies for the treatment of solid tumor cancers. As you know, Ren, solid tumor cancers are 90% of all cancers. We have a platform, a cell therapy platform, that's based on a T cell known as the tumor-infiltrating lymphocyte, or TIL. And our platform provides patient-specific products, individual products, for cell therapy patients with solid tumors, based on isolating and expanding the TILs from patients' tumors. We have a proprietary process. We've been working on it for many years.
We've treated over 700 patients, and we're very proud, and everybody who follows this field knows that in February we received the first in class, the first approval from the U.S. FDA for a cell therapy for solid tumor cancers. The product's called Amtagvi, and our immediate priority is the commercial launch of Amtagvi in the United States. This is a significant unmet need. The product was approved in metastatic melanoma, post-PD-1 checkpoint therapy. So second-line metastatic melanoma treatment with our product Amtagvi. And this is significant opportunity, and we're very pleased to say that the launch in the first 3 months, since the approval in mid-February, is going extremely well.
We had a conference call on Thursday night, our first quarter conference call, and we reported on the launch with several metrics that I'm sure we'll discuss this afternoon. We're very pleased to see that the significant unmet need is being well-addressed with our cell therapy initially right after approval. Our strategy beyond managing the commercial launch this year is really threefold. We want to increase TIL therapy into other indications, namely lung cancer and endometrial cancer. I'm sure we'll talk about those new indications as well. We want to increase TIL therapy for treatment of front-line patients. Right now, our approval, as I mentioned, is in second-line patients in the United States, but we want to take TIL forward into front-line therapies, and we have a major...
the largest phase lll, or one of the largest phase lll cell therapy trials ever conducted now in frontline metastatic melanoma being conducted globally. And finally, we want to bring next generation TIL products to the forefront. We have several under development. We have a PD-1 knockout in the clinic. We just announced an IL-12, a tethered IL-12 TIL, that we're working on, and we'll bring to the clinic next year. And we also have a second-generation, IL-2 product as well, that we expect to file an IND on shortly.
Yeah, so I mean, one of the... I mean, A, congratulations, right?
Thank you.
On the approval, the launch. It's a big deal in biotech, right, in general, to go from development to commercialization stage. A lot of companies don't, you know, get a chance to do that. We know what the failure rates are like, and so this is a huge deal. Let's talk a little bit about the launch and how it's going. What kind of metrics, you know, can you tell us to give us a sense as to how things are progressing? I know you guys mentioned it on the call, which you just had last week, but maybe the flip side of that is, you know, what kind of challenges are you seeing in the launch? I imagine largely anticipated, but what are you seeing?
Yeah, so first of all, we're very pleased with the initial launch metrics, right? What we spoke about last week on the conference call is that we have many authorized treatment centers already positioned and authorized in the United States to treat TIL patients. We are guiding towards 50 authorized treatment centers by the end of May. So we already have the sites where patients can be treated well-established. We also guided that right now we have 100 patients enrolled in various sites for TIL therapy, and we have an additional 60 patients in screening. And what we're seeing is month-over-month increases in the number of patients that enter screening and that become enrolled.
So everything is very positive in terms of, you know, the metrics that you and I might look at to gauge the strength of the launch. The other very important piece of this, and this could have been a challenge so if you look at historically, cell therapy launches in the United States, I think you and I would focus on a couple of different challenges that cell therapy companies have had. One is reimbursement, right? Having the financial infrastructure for, to, provide for patient access in place at the time of launch. And we gave some, again, some metrics, on the call the other night that we have 13 payers covering 90 million lives already with coverage policies in place.
So there's a lot of momentum in the payer piece of the puzzle, right, for a successful launch that's already in place. We also have payers covering 200 million lives already having at least one patient in the queue. So in terms of traditional challenges that you might look at with respect to our launch, the reimbursement piece of the puzzle, I think, is well in hand, and we have the metrics to show that. The other challenge that cell therapy companies have showed is capacity.
Mm-hmm.
Right? Is having enough manufacturing capacity in place at launch to handle demand, and again, we spoke about that last week, where we have two. We're fortunate to have two manufacturing sites available to us at launch. One is our own manufacturing site, known as ICTC, and the other one is our CDMO manufacturing site, which happens to be right across the street. And at those two sites, we have ample capacity in place to handle the demand that we see, certainly right at launch and throughout the rest of this year going into next year. And we're beginning to ramp up our own hiring efforts and our own capacity space build-out in anticipation of what we believe are the accelerants that'll come into, into the number of patients that we treat over the next 12-24 months.
So we have another, another issue that you might expect, another challenge that you might expect, well-addressed by virtue of the fact that we have these two manufacturing sites that are ready with ample capacity.
Fair enough. Can you give us a sense as to the split between the commercial and government sort of payers, you know, you might be experiencing right now, and what you might expect going forward?
Sure. Initially, I think we mentioned the other night that more than 75% of our patients are being covered by commercial payers. Whether that will hold remains to be seen, but at least initially, what we're seeing is 75% of the patients are covered by private insurance.
Can you give us a sense... I don't, I don't know if since the call you've talked about this, but how many patients have been treated to date? I don't know if you guys, you know, mentioned that. And then, as you think about the patients, you know, can you give us a sense as to what kind of patients are these? How many prior treatments? Is it pretty much being followed as the label dictates, you know, post-PD-1, kind of nth stage patients, or are you starting to see, I know it's early, maybe even some movement to slightly upstream in the, you know, in the treatment paradigm?
Sure. Well, the guidance that we've given are the numbers that I've mentioned, right? 100 patients enrolled, 60 patients in screening. And again, there was more discussion on the call last week that said that those patients are going to be treated in the second and third quarter of this year, right? So that's what's out there in terms of patients treated. In terms of the patients that we're seeing and that we expect, ultimately, you know, I think the patients are going to align with a couple of things. They're gonna align with the label-
Mm.
... right? We have a second-line label, post-PD-1. They're gonna align with treatment guidelines. So one of the positive things that happened in the last, you know, six weeks since launch, is that we got put on the NCCN, National Comprehensive Cancer Network, guidelines, as the treatment for second-line melanoma. And then finally, payer policies, right? So I think all of those are gonna drive label, NCCN guidelines, and payer policies are gonna drive what we see in terms of the patients that get treated with Amtagvi. Now that the drug is out there, there's always opportunities. We have a broad label. We already have a broad label, right? But there's an opportunity to treat patients later line, of course, and there's an opportunity to treat patients earlier.
However, I think the patients are ultimately gonna align across label, payer policy, and NCCN guidelines.
Gotcha. So let's talk about ICTC, or sorry-
ICTC.
ICTC-
Yeah
... thank you.
Yeah.
Expansion efforts.
Yeah.
I think you mentioned that you'll be at 70 by the end of this year?
70-
Maybe I'm thinking ATCs, is that-
Yeah, 70 authorized treatment centers.
Authorized, yeah.
That's right. That's right.
ATCs.
That's right.
And so, you know, I guess maybe I wanna switch it back to ICTC-
Yes
... expansion efforts. Can you just kind of talk us through that?
Sure.
Maybe a little bit of the plan for European filing as well.
Sure
... and how your manufacturing, you know, kind of capabilities address that European filing as well?
Of course, of course. Yeah, right now, ICTC, which is our plant, has the capacity, the built capacity, to handle 2,000 patients. As I mentioned, we're ramping up our hiring efforts with technician, in line with demand. As we see increasing demand, we're hiring those technicians, to be able to make sure we have ample capacity to meet that demand. Now we established this facility to treat multiple thousands of patients a year, so the next build-out for us is to go from 2,000-5,000 patients a year, which will require some construction. We've already pulled the trigger on starting that process in terms of the expansion of space that we have, to make products at ICTC.
And then ultimately, beyond 5,000 patients a year, we have options on additional real estate right around our plant that would allow us to go to 10,000 patients a year at that site. In addition to that, we have expansion capacity and flexibility provided by our CDMO. So as I mentioned, there's ample capacity, and we have the room to grow, and are right now hiring in anticipation of that growth. How that relates to the European and ex-U.S. strategy is that initially, we have the vision to manufacture products for patients outside of the U.S., also in the U.S., envelope that we have in Philadelphia. We believe that it's possible to get the patient's tumor to Philadelphia. We know, we don't believe, 'cause we've done it in clinical trials-
Mm-hmm
... to get the patient's tumor into the Philadelphia sites, and then get the product back, especially since the product is now frozen, which is really important in terms of delivery back to the patient, you know, across the ocean, and do it in time to get the patients, you know, treated, as quickly as possible.
Gotcha. We hear a lot about the Biosecure Act.
Mm-hmm.
Your CDMO is WuXi. So I guess, you know, can you give us a sense as to how this may or may not, you know, impact your CDMO, and do you have a backup to your backup?
Sure. One of the main reasons that we built our own plant, and we made a commitment to do it as early as we did, is that especially in the autologous cell therapy space, you know, manufacturing is at the core of everything, and controlling your own destiny in terms of having your own plant is critical. So, as we said last week on the call, as I mentioned just now, the bulk of our commercial manufacturing to date, and this is also gonna roll forward, is gonna be out of the ICTC plant.
Right.
Out of our own facility, right?
Mm-hmm.
What's useful about our CDMO is that it's really the flexibility that having them offers in terms of being able to offer, you know, additional manufacturing slots on particular dates, things like that. That flexibility is valuable as well as the additional capacity that goes with that flexibility. Having said that, you know, we plan on having the bulk of the manufacturing done by ICTC. We're scaling up ICTC to address the, you know, the increased demand that we see out there in the marketplace, and therefore, we don't believe that the Biosecure Act is a factor in terms of our ability to meet demand.
Okay. So we'll switch gears to a presentation that's coming up, the ASCO presentation that's coming up.
Yes, sir.
Right? 'Cause you have the commercial launch that's ongoing in melanoma.
Yes.
You have the phase lll study, confirmatory study, TILVANCE, which is ongoing, that could ultimately move this front line.
Mm-hmm.
So melanoma seems to be, like, tied up in a nice... with a nice little ribbon around it. I know, I know I'm simplifying it. There's a lot, lot of work to be done, but it's well on its way. But you have a pipeline that you're developing, right? You mentioned non-small cell lung in your intro comments, endometrial. We're getting some non-small cell lung cancer data by ASCO. Can you give us a sense, how many patients worth of data? What's the kind of, you know, metrics or, or meaningful update that you're looking for, or you're hoping investors gain from, from this update?
So you're talking about this ASCO, right?
This coming ASCO.
It's melanoma data.
Oh, yeah.
That, that-
Sorry, did I say non-small?
Yeah, yeah.
Sorry, melanoma data.
It's melanoma data.
Go on.
Yeah.
Okay.
What we're doing is we're updating our combination single arm trial, where we combine TIL with the PD-1 checkpoint, right?
Mm-hmm.
This trial that we're reporting on at ASCO is really the supporting, you know, rationale for our big phase lll frontline trial with 670 patients to be enrolled. So it's really the underpinnings of why we feel so strongly about the opportunity for TIL in the frontline space. Historically, we've reported on, I think, 10-12 patients. The updated ASCO is gonna be significantly more than that. And you're gonna get visibility into the things that are important, right? Which are the ORR and the duration, and time that those patients have been on study.
Okay. I know, I know why I mixed up the lung and melanoma. The questions are right next to each other. So now let me hit you with lung.
Yes.
The clinical trial hold was lifted-
Yes
... right? You know, what, when should we be expecting data from this study, right?
Yes.
Now that it's, you know, back to being enrolling, when do you think enrollment will complete?
Yeah, first of all, we're really pleased with the fact that, you know, I think people know that this clinical trial in lung cancer, our registrational trial, was put on clinical hold near the end of last year. But we came out of that partial clinical hold very quickly with the FDA. We had excellent collaboration with the FDA on the safety issues that they identified, and we presented them with a plan, let's say a plan to move forward addressing those safety issues.
Mm-hmm.
And we came out of the clinical very quickly. And I think the KOLs and the sites that we have already invested in that trial remain very excited about that trial, eager to put patients back onto accrual. And so what we've said is that we anticipate full accrual of that trial at some point next year. Obviously we know there's great appetite for information around that trial. So we will provide an update when it makes sense to do it. Obviously, you have to be judicious about, you know, registrational trials, and how you provide, or how much data is provided in anticipation of registration or filing, and getting the drug registered.
But we know there's great appetite, so we will update as soon as it makes sense, when we have enough patients and enough visibility on the trial. And also making, you know, balancing out that registrational point about making sure we present the right data at the right time.
So when we think about the pipeline, as we think about, call it Iovance's playbook-
Yes, sir.
... does it make sense to just say, "Look, they did it with lifileucel in this way," right? Post-PD-1 checkpoint, then their confirmatory study is frontline.
Yeah.
Is that the way we should be looking at non-small cell, then, what would be the next program after that?
Endometrial.
I guess endometrial, okay.
Yeah. Yeah. Yeah, that is, right? The strategy, melanoma was, you know, second line approval, followed by, you know, frontline combination. Non-small cell lung cancer, LUN-202 is a second line post-PD-1 checkpoint trial. We've presented great, frontline combination data with pembro in non-small cell lung cancer as well, so you can anticipate us... And we already have a trial design for a phase lll frontline trial in lung cancer as well. Accelerated approval, right, first, second line, and then moving to full approval with your frontline trial reading out, over time. And endometrial is gonna follow the same playbook.
What's interesting, and we talked about this, and actually you asked a question about it last week, is that the melanoma playbook informs our ability to get lung cancer, and endometrial, and, and other solid tumors approved, because of the way we are now engaging with the FDA. We talked about the potency assay.
Mm-hmm
... with respect to the lung cancer trial last week. And yes, we obviously have the playbook from the melanoma experience, and we're, you know, making sense from that playbook in terms of accelerating the discussions with the FDA with respect to potency assay for the lung cancer indication.
Kind of in the last couple of minutes that we have left. I always enjoy our talks. They always go by too quick. You know, the key drivers for Iovance Biotherapeutics in the next, you know, call it for the rest of 2024-
Yes
... and importantly, what's the cash position? I know you guys just reported it, but, you know, there's always this nexus, if you will, right? When you're starting commercialization, the spend is huge, the ramp is typically, you know, kind of slow, and so you really have to manage your cash position pretty well. So how long does that cash last?
Sure. So, 2024, we're laser focused obviously on the launch, and demonstrating, you know, what we see, and executing against the unmet need opportunity, and delivering Amtagvi to as many patients over 2024 as we can. And also providing the right, you know, accelerants to that whole process. For example, one of the things that we're doing is, we have a program to focus on community patients, and to drive them to the ATCs.
Mm-hmm.
So you can think of that as the ATCs, as more and more ATCs come online, as more and more, ATCs scale from one patient a month to three, four, five patients a month, that's an accelerant. And then another accelerant is, a program that we have to drive patients from the communities into the ATCs, to have that third, accelerant, happening throughout this year. So that's, that's, the primary focus, I would say, for 2024. But equally important, because it puts in place the pieces of the puzzle for 2025 and 2026, are the registrational filings, right, outside of the U.S., in the EU, in Canada, and in the U.K. So by making those filings in 2024, right, we're gonna be in a position in, 2025 to have those next accelerants coming in to the commercial ramp-up.
And then beyond that, it's important for us to accrue LU-202.
Mm-hmm
... and to accrue TILVANCE-301, right? That's the lung cancer trial and the frontline melanoma trial. Because by putting patients on those trials, having the data read out, that provides the next wave of growth into 2026, 2027, right? One of the interesting points that I wanted to make sure I made about TILVANCE-301, you're aware of this, is that, there's an interim read. There's an interim read with respect to ORR on that trial-
Mm-hmm
... right? Which allows us, right, to get, in a sense, the registrational answer sooner from that trial. So stay tuned as we accrue patients on TILVANCE-301, because, you know, the frontline data is already very interesting. We're gonna update that data at ASCO now, right? And then we have the opportunity to have an interim read based on ORR, which could be, again, another accelerant going into the 2026, 2027 timeframe.
Yeah, so one day we'll get a chance to discuss, you know, how this impacts community versus academic centers, right, and how that mix can grow, but unfortunately it's not today. Cash position, and how long you think that cash position-
Sure. We reported $360 million in cash, and the fact that we feel great about the cash position, it takes us late into next year. That, of course, includes the revenues that are gonna be coming in from Amtagvi and Proleukin. We're a very fortunate company, in that, you know, we've always had access to the capital markets. We have a great financial team. They're very smart about raising money efficiently. And so at the right time, in the right place, I'm sure that they'll make the right decision and add cash to the balance sheet.
If not with the right partner.
There you go.
Thank you very much, Jean-Marc Bellemin.
Thank you.