Okay, good morning, everyone, and welcome to our next session. I'm your moderator, Sarah Nik, and I'd like to present our next presenters from Iovance Biotherapeutics. I'd like to welcome Igor Bilinsky, COO, and Brian Gastman, EVP of Medical Affairs. Iovance Biotherapeutics develops tumor-infiltrating lymphocyte therapies against cancer, and with that, the floor is yours.
Morning, everyone. Good to be here. So, as part of this presentation, we'll be making forward-looking statements, and I refer you to our SEC filings for a full disclosure of risks and uncertainties. So Iovance, we're a global leader in innovating, developing, and delivering TIL, a tumor-infiltrating lymphocyte, cell therapies for patients with cancer. We have two approved products. One is Amtagvi, which was approved in February this year. It's the first T-cell therapy approved by the FDA for a solid tumor cancer, and it's approved for patients with advanced post-PD-1 melanoma, and the second product is Proleukin, which is IL-2, which is used as part of the Amtagvi treatment regimen. Right now, we're very much focused on the commercial launch, which is going very well. We've launched with 30 authorized treatment centers.
We have more than 50 right now, and ramping that up to 70 by the end of the year, and this is a very significant market opportunity. More than 8,000 patients in the U.S. and more than 20,000 patients with advanced post-PD-1 melanoma is the addressable population in the markets we're targeting globally. In addition to Amtagvi and Proleukin, we have an extensive pipeline that includes two pending regulatory submissions in the EMA in particular, that we filed this year, and it was validated by the EMA in August, and we plan to file in Canada and the U.K. later this year. We have two registrational clinical trials ongoing. We have a total of eight clinical trials in seven different tumor types.
On the financial side, we had a cash position of $450 million as of July 24th , and that's, we expect, sufficient to fund operations into 2026. Strong team, very focused, very dedicated, with about 700 employees today, and also, as part of the recent Q2 call, we provided revenue guidance both for this year and for next year, and the guidance for 2024 is between $160 million and $165 million in total revenues for Amtagvi and Proleukin, and the guidance for 2025 is between $450 million and $475 million in revenues. This is an overview of our pipeline. Again, two approved products, Amtagvi and Proleukin. A registration-directed study in frontline melanoma, combination of lifileucel and pembro. That's our TILVANCE-301 trial.
There's a registrational trial for second-line lung cancer, IOV-LUN-202, for patients with advanced post-PD-1 non-small cell lung cancer. We are also initiating a study for patients with endometrial cancer, and the next-generation pipeline includes our IOV-4001 product, which is a PD-1 inactivated TIL, that has successfully completed a safety phase I section of the trial and is now in the multicenter phase II. We also plan to bring IOV-3001 product into the clinic shortly. It's an IL-2 analog, that could be next generation IL-2. And finally, not last but not least, we've announced IOV-5001. That's in pre-clinical IL-12 tethered TIL, which we believe to be very promising, and we have an IND planned for that next year. Our company will look to address very significant market opportunities and very significant unmet need.
More than 90% of all cancers are solid cancers, solid tumors, and about 1.8 million new cases of solid tumors are reported annually in the U.S.. The number of deaths from the initial indications we're targeting, 8,000 deaths in the U.S. from melanoma, more than 100,000 deaths from lung cancer, 13,000 deaths from endometrial cancer. Focusing on melanoma first, there are about 20,000 patients in the addressable population for the initial approved indication of Amtagvi globally, and that includes about 8,000 patients in the U.S. and additional about 22,000 annual deaths in the ex-U.S. markets. As a reminder, we have approval in the U.S. We filed for approval in Europe this year, and that submission was validated in August by the EMA.
We plan to file in the UK and Canada in the second half of this year, and then Australia and Switzerland next year. So I'll turn it over to my colleague, Brian Gastman, our Head of Medical Affairs, for the next section.
Mm-hmm. So, this is sort of to remind everybody that this is a personalized, individualized therapy. This is made from the patient's own tumor. And in terms of what we are giving patients that is now FDA approved, this is based on the LN-144 trial. And that trial, which Cohort 4 within it led to that approval, had an overall response rate of 31.5%. And I think most importantly to the field, to physicians, patients, is that the duration of response has not been reached. This trial is multiple years in activity. It's nearing its end, actually. And to have such durability is sort of unheard of in a group of patients that have already failed what was already a very disruptive frontline therapy paradigm.
So, this was also supported by our Cohort 2, and then combined, and as mentioned in our label, you can see the response rate's essentially the same, and the mDOR is still not reached. So for all these reasons, this is a very easy drug to discuss with patients and physicians because of the promise that it can afford in a population that heretofore really had nothing else to give them, as these had already failed all of our standard lines of therapy. I know that you probably,
I can touch on this one, so-
Yeah, let me give this one over to you.
Manufacturing is a core capability for us, for Iovance, as, of course, our therapy is an autologous cell therapy. To fully control our destiny, so to speak, we built our own manufacturing facility. We call it the Iovance Cell Therapy Center or ICTC. It's located in Philadelphia, and it's one of the largest cell therapy facilities in the world, and it's the only one that's been designed specifically for TIL cell therapy manufacturing. And again, it allows us full control of our manufacturing capacity, quality, and turnaround time, everything that's important to have if you have your own manufacturing facility. Currently, ICTC is built for capacity of over 2,000 patients per year, and we're now staffing up our team to match capacity with demand and growing the actual capacity every month by month.
As part of the same building, we have shell space that we're now starting to build out, and that will bring the capacity to more than 5,000 patients per year in a couple of years. And then the next step in the evolution, we're planning to further expand the ICTC campus. There's an adjacent lot for which we have an option to build another manufacturing building. And that, together with automation of the manufacturing process, we expect to bring the total capacity for Amtagvi and TIL manufacturing to more than 10,000 patients annually from that campus. And as far as the launch, as I mentioned, we launched initially with 30 authorized treatment centers, or ATCs, in the U.S., and we've already ramped that up to more than 50, actually 51, as of August this year.
By the end of the year, we plan to bring the number of ATCs to about 70 in the U.S. The reason for that is we'd like to ensure that it's convenient for the patients to receive Amtagvi, and the idea is to have 90% of addressable patients be within 200 miles of the nearest ATC. As far as the launch, again, the launch is going very well. We're very happy about that. Some of the metrics here, more than 75% of Amtagvi patients are covered by private payers. Today, the payers have coverage policies in place that cover more than 225 million covered lives, so that's been going very well. The time for financial clearance has been accelerating since launch.
We started, it was typically about four to six weeks for the ATC to receive financial clearance from the payers. Today, it's been reduced to about three weeks, and it's been compressed further as ATCs and payers get more experience with the product.
Of course, we don't just live on our laurels. Igor mentioned our, our, sort of, long-term pipeline, some of the really exciting products. But what's currently going on in our clinical trial portfolio starts really in advancing what we're doing in melanoma. If anyone was at ASCO, you would have heard about our 1A data, our COM-202-1A, 1A data, which is in frontline melanoma combination with pembrolizumab. What was exciting there wasn't just the fact that in this phase II trial, we had a 65% overall response rate, was the ratio of complete responses to PRs. Usually, these numbers are completely driven by the PR side of things, and almost half of that ORR was driven by the CRs. We know historically that CRs can lead to even decades-long TIL outcomes, positive outcomes.
And so while this is still a relatively early snapshot of what we've seen, this is highly encouraging. And you can see with the swimmer's plots, the kind of durability we're seeing and that we're continuing to see from these patients, as this is an ongoing group of patients being evaluated. Those waterfall plot at the top right gives you a sense of the kind of responses, and you'll note that there's not a single patient there that the waterfall is upside down, right? They're all down. So you go from SD, essentially, to CR.
So this is a really strongly controlled group of patients, and it is one of the reasons why when we went to the FDA, when we discussed how we're going to do our confirmatory trial to get full approval of Amtagvi, they allowed us to go into the front line with what's called TILVANCE-301, or TILVANCE, which is our global phase III clinical trial, comparing TIL plus pembro or lifileucel plus pembro versus pembro alone. It's important to note that patients start off with pembrolizumab regardless of their ultimate assignment, and moreover, if a patient on the pembrolizumab arm fails, they can switch over to TIL. It's important because many of the patients who would go on such a trial want the TIL side of it, and so they have the opportunity to get it regardless.
But the goal is to evaluate arm A versus arm B, and with—you see that kind of data that I just showed you in the previous slide, we are expecting a very large delta. At a minimum, this is to support and validate our second-line approval in Amtagvi, and at a maximum, this could potentially lead to disruption of how we treat frontline patients. Now, in terms of the other major area, Igor mentioned the huge opportunity for non-small cell lung cancer. It's actually the most common solid tumor in the United States. It leads to around 15 times-
... the number of deaths that we see in melanoma, and it's similar to melanoma, though the frontline is a PD-1 backbone therapy with chemotherapy. Unlike melanoma, though, many patients do fail in the frontline, even at a higher rate than we see in melanoma, and currently, really, there isn't a great second-line therapy, and certainly, the second-line therapies are given, have very low duration, so you can imagine now, if we can offer something that has a reasonable response rate with great durability, that could significantly impact a larger number of patients, and what you can see on your right is that impact, not just in the United States, in the second- and third-line, which is what we're looking at right now, but also ex-U.S. as well.
So there's a very large patient population that's in dire, desperate need for therapy. We have our registrational trials. Think of it somewhat like our LN-144 that led to Amtagvi approval. In lung, this is an international trial. It's accruing as we speak. We do hope and anticipate, as you can see at the bottom, to complete it in the end of twenty twenty-five. And of course, as soon as we can do a data cut that makes sense, we will present that data in the near future. We're very excited to be able to present this because of the data that we've already discussed in our press releases last year. We're expecting some, you know, continued strong data to support the ultimate approval of this drug as well.
And in that vein, this is the type of data you would see in our press releases. The waterfall on your left, you can see the vast majority of these patients. Remember, these are patients who are lung cancer, not melanoma. They're in the second line. You can see the type of, the effects, that the vast majority are going down, and on your right, again, you're seeing great durability. I mean, patients are still swimming along in their swimmer plots. That's what we wanna see. That's what we don't have right now in the field, treating these patients. And then we also mentioned earlier, endometrial cancer. If you think of it, that lung is one step behind melanoma, then endometrial is, like, one step behind lung. We're using a very similar playbook because of the similarities.
Here's another cancer, heavily treated in the upfront setting with the PD-1 backbone therapy. Again, like lung, combined with chemotherapy, a lot of surgical aspects, like melanoma, like lung, and so if you're going to do something similar in a group of patients that don't have really anything in the second line, we can follow a very similar playbook that has worked well and has been in good, strong concert with the FDA, and the plan, again, is to lead a second-line-based therapy for these patients that have failed chemo and anti-PD-1 based therapies, which are approved actually in both the MMR deficient and proficient. Some only in one and not the other, but others for both, and well, our plan is to look at both.
So we're gonna look at a wide spread of these patients, and the plan is to do something similar, as I've just showed you. And with that, I'll leave the rest for Igor.
As of July twenty-fourth, we had $450 million in cash and cash equivalents on the balance sheet. We're well-capitalized in pursuit of our TIL commercialization and developing our pipeline. This cash position we expect to be sufficient to fund operations into 2026. In summary, 2024 is a big eventful year for Iovance. We received FDA approval for lifileucel or Amtagvi. Again, first T cell therapy ever approved by the FDA for a solid tumor cancer. We received approval on February sixteenth this year. We are actively commercializing. The launch is going very well. We're very happy about that, and we've provided revenue guidance.
As planned, we submitted the application for approval in Europe, in the E.U., in the first half of this year, and that was validated by the EMA in August, as expected. We plan to submit additional ex-U.S. filings later this year, including the U.K. for MHRA, and also in Canada, and then additional filings are planned for next year in Australia and Switzerland. Finally, another milestone, we plan to meet with the FDA this year to discuss the non-small cell lung registrational and the frontline study in lung cancer. On the pipeline side, we've reported very exciting data at ASCO that Brian mentioned in frontline melanoma, that showed a 65-66% response rate and a complete response rate in the 30% range, which is very, very promising and rather unheard of in that setting.
We've resumed enrollment of our registrational study in lung cancer, IOV-LUN-202, and with the endometrial phase II cancer study is now underway. We are planning to continue enroll our pipeline trials through the rest of the year and advance new products into the clinic, including our IOV-5001, IL-12 tethered TIL, which is now in preclinical development, could be next-generation product for us. And finally, on the commercial side, we already mentioned, we're executing commercial launch. That's going very well. We started the launch with 30 authorized treatment centers at approval. We are now at 50, as we had expected, within 90 days of approval, and we plan to bring 70 ATCs on board by the end of this year. I will conclude here and leave room for some questions. Thank you.