Hello, good afternoon everyone, and thank you for joining us for our next session. My name is Matt Keller, I'm a VP here at Wainwright in the Research Department, and next we're speaking with Iovance Biotherapeutics. With us to speak about Iovance, I have Jean-Marc Bellemin, the CFO of Iovance, as well as Peter Prieto, excuse me, SVP of Medical Affairs. Welcome to both of you, and thanks for joining us.
Thank you. Thank you for having us today.
Yeah, absolutely. So first off, I wanted to give a big congrats to Iovance and then two of you for the recent approval of Amtagvi. Obviously, a huge milestone not only for the company but for what we think to be TILs and cell therapies in general. Obviously, we're a little bit more familiar with this story, but to kind of just start off, I wondered if you could give our audience a little bit of a high-level overview of TIL therapy, you know, its applications, as well as its potential in the space.
Yeah, thank you for that question, Matt. I think it's good always to, you know, set the stage about TIL cell therapy. So TIL is a new cell therapy approach that deploys patient-specific T cells called tumor-infiltrating lymphocyte, or TIL, cells to fight cancer. And it's a one-time treatment that is manufactured using a manufacturing proprietary process Iovance has to collect, isolate, and actually multiply patient-unique T cells from a portion of their tumor. And, you know, let me briefly describe how it works. When a cancer is detected, the immune system then creates T cells to locate, attack, and destroy cancer. T cells will recognize the distinctive tumor markers on the cell surface of each person with cancer. But when cancer develops and prevails, the body's natural T cells can no longer perform their intended function, and that's how TIL cells are critical.
Iovance TIL cell therapy returns billions of the patient's T cells back to the body to actually fight the cancer. Unlike any other cell therapy approaches that target shared antigen among patients, TIL cell therapy is individualized for each patient based on their own unique antigen. It's, you know, a nice new tool that will be used in solid tumor.
Yeah. You know, and you brought up the individualized side of the product, which we also think is a huge part of our investment thesis for TILs and Amtagvi. But one thing we've noticed, and we'll dig a little bit deeper into some of the clinical data later, but, you know, one thing we've noticed is both safety and durability of the product as well. And, you know, one of the phrases we like to use is "magic saw." So I wonder if you could maybe talk a little bit more about what makes lifileucel or TIL therapy, you know, so effective but also safe and durable as well, maybe compared to some other products on the market as well.
Yeah, I can speak to that. So, you know, when we talk about TIL, we're talking about a non-gene-modified living treatment, cell therapy that comes from the patient's tumor, that know to go to the tumor. It's really, in many ways, one of the most perfect personalized immunotherapies. And Iovance TIL cell therapy has evolved from an approach that academic centers and the National Cancer Institute have successfully used for a small number of patients for years. But we're able now to scale that up. And again, seeing that TIL, a non-gene-modified cell product that doesn't use viral vectors, has little to no off-target toxicity. We've treated now in our clinical trials more than 700 patients with TIL cell therapy manufactured and scaled from our proprietary processes.
So we're very confident that this is a very safe and durable and a living cell therapy, and we see deepening of responses that you don't see in other cell therapies. So we're very excited about that.
Yeah. And I think all those things kind of bring us to, as I mentioned kind of in the introduction here, the recent approval of Amtagvi and the post-anti-PD-1 advanced melanoma indication. Obviously, the FDA heard that as well. But obviously, the journey to that approval was a bit of a process. I was wondering if you guys could maybe review its clinical journey as well as some of the insights or lessons learned on the journey to approval for Amtagvi.
Yeah, let me take this one, Peter. Thank you, Matt. Indeed, I mean, we can say it was a little bumpy to get approval, but we succeeded to bring the first cell therapy to treat solid tumor. So I think we're super excited about that. And so your question about what was the, you know, sum of the lessons learned along the way, I think first for us was a need to understand the unmet need, the treatment landscape, and of course the patient population, which should help to define, you know, what was the design of the multi-center clinical trial we had. I think we also were clear about the fact that having an active and regular dialogue with the FDA throughout the clinical development and also while defining the regulatory pathway, especially when you bring the first-in-class agent to the market, was critical.
I mean, you need to stay close to FDA all along the way. I think we also agreed to say that it was critical and very important to us to invest in manufacturing as early as possible in advance of the regulatory approval and to make sure that we had a CMC section that is robust enough to go with the BLA submission at the start of the review process. I mean, that was definitely critical for us. Now, if you think about lesson learned post-launch, I think we're clearly benefiting from the pre-approval onboarding of what we call ATCs, or Authorized Treatment Centers, which clearly allowed us to have an unprecedented number of centers ready to go at day one. I mean, we say we had 30 at day one, moving to 50 within 90 days.
This will be clearly a differentiating factor for us to be successful with the launch of Amtagvi.
Yeah, and you're kind of already—this is a nice segue into my next question. You know, we're very familiar, again, with the amount of time, effort, and investment that Iovance has put into preparing for launch. You mentioned getting those ATCs on board too. We also know you have a fantastic new facility as well for production. But I was wondering if you could maybe comment or give a little bit more detail on other efforts you've put into preparing for the commercial launch and kind of the steps going forward that we'll probably see in what the next six months to a year to really get Amtagvi out there.
Yeah, so I mean, let me take this one, Peter. Let me highlight some of the, you know, key components of our commercial readiness effort to ensure really a successful launch. I mean, first, I think we had the first—we have the field team in place to support our ATC from the get-go and for their initial patients. So there was a clear focus on the successful first experience because this helped to further facilitate future adoption at the level of ATCs. And, you know, we continue to open new ATCs. That's also critical. And as I just mentioned, moving from 30 at launch to 50 within 90 days. So you can reach out to the patient and you can help the ATCs to enroll patients and be successful there. That's clearly something that will be critical and is and was critical to prepare for us for successful launch.
We can see, I mean, ATCs are moving patients through the journey with a clear sense of urgency. You know, as an example, the first surgery was scheduled on the first business day after approval. Of course, you imagine our people who are just expecting for Amtagvi to be approved and to be available for the patient. We can say now that the majority of our ATCs have identified at least one patient with even several centers already providing multiple patients and commenting on manufacturing. Manufacturing is underway for commercial patients, and we have said multiple times, we have plenty of capacity to fulfill our current and expected initial demand. I think that's important to highlight all of that as part of the effort we put into the successful launch.
Yeah. And again, Jean-Marc, I think you're kind of reading my mind a little bit, but, you know, it's only been, what, almost a couple of months since the approval. But I was wondering, I realize this is kind of early, maybe getting ahead of ourselves, but, you know, can you speak to the reception of Amtagvi thus far, potentially some physician anecdotes or outreach that you're receiving from the community as this product, again, begins to infiltrate the market more and more?
Yeah, I can take that one, Jean-Marc?
Yeah.
Yeah, I can take that one. So as a former surgical oncologist coming from academia and joining the medical affairs team at Iovance, I can tell you that this has been a long wait. People, patients, healthcare practitioners have waited 38 years for this to come out of the NCI. Remember, although CAR-T came to the market before TIL, TIL predates CAR-T in terms of innovation, and we've known that this therapy can be very effective and durable. We've had a lot of community reception in a very positive manner. As Jean-Marc mentioned, the first surgery was essentially the next business day after approval. Not only are we seeing patients being identified at all of our onboarded ATCs, but at many of the sites, we're seeing multiple patients, and we're seeing referrals from outside the ATCs.
Centers that don't have the ability to give cell therapy but are now hearing about the approval of Amtagvi are sending these referrals. We're getting these inbound interests from non-ATCs about not only sending patients to authorized centers, but how do we become an authorized center moving forward? What's also very exciting is the first patient, and this was on social media, which was resected at Stanford, was really scheduled in parallel with financial clearance. Centers are confident about their ability to move forward with this across multiple workflows and systems in place. We're very excited, and the demand is very much present.
Somewhat related, but backtracking a little bit too, I think when it comes to reaching these patients and doing so effectively, I think another huge pro of Amtagvi is also the vein-to-vein time as well, the ability to get to the TILs and also get them back into patients in an expedited manner that has to do with the commercial preparedness as well as all the preparation you've done thus far. I was wondering, is that also a component in consideration? Is that something that is also brought up as well when people talk about maybe selecting Amtagvi as their treatment of choice?
Very much. We have the ability, again, we have a proprietary manufacturing process that is successful well over 90% of the time for 22 days. And what we talk about tumor tissue procurement to infusion, we have a process of about 33-34 days, which includes that 22-day processing, manufacturing, and then some quality checks and shipping. And our centers now have the ability to line up and go into our standard of care, proprietary Iovance Care system, to enroll and schedule these patients. And we are finding that the centers are very much feeling that this is very user-friendly and very patient-oriented.
Yeah, fantastic. Thank you. Thank you for that additional color. You know, again, I have to give a big congrats to you guys for Amtagvi. Again, we think it's a phenomenal milestone for the space and for you guys as well. But I also know there's other things cooking in your pipeline as well. We talked about advanced melanoma for Amtagvi, but I was wondering if you can maybe move down the pipeline a little bit and talk about some of the other clinical trials and the other indications, particularly solid tumor, that you're looking to apply TIL therapy into.
Yeah, I mean, let me talk a little bit, and then Peter maybe just can highlight a little bit on some of the clinical program. But we know that, you know, the same manufacturing process can be leveraged across solid tumors. And applying what we have done in melanoma to other solid tumor indications is, of course, something that we're working on. Assay matrix for commercial release testing in melanoma can also be used as a template for subsequent indications. If you think about it, Iovance TIL cell therapy has been approved for patients as the first treatment option after anti-PD-1 therapy. And there are other solid tumor indications such as, you know, NSCLC, endometrial cancer we talk about, where TIL cell therapy can definitely potentially benefit patients after anti-PD-1.
So each indication has unique unmet needs, available care that requires a specific approach to our clinical development program, regulatory pathway, commercial opportunity. But we are definitely planning to target these unmet needs and excited about the opportunity. So again, I'm sure Peter can comment more about our clinical pipeline and go further if you want to.
Yeah, I think so.
Yeah.
Oh, go ahead. Sorry, Peter. Go ahead.
Sorry. I was going to say another exciting aspect of our clinical pipeline is not just TIL beyond the melanoma indication, as Jean-Marc mentioned, but even when we look at melanoma and non-small cell, we have a PD-1 inactivated TIL product, our IOV-4001 platform, that really is a PD-1 inactivated knockout. As a commercial company with a late-stage pipeline, we have a lot of efforts in this space. This next generation of TIL seeks to not only enhance efficacy but potentially abrogate the need for checkpoint in conjunction with TIL by knocking out the PD-1 gene. So we have the ability to develop potential best-in-class TIL as we move forward. The IOV-4001 currently is completing phase I portion. This is a first-in-human trial, and we look to soon expand that to phase II, both in the melanoma and non-small cell lung cancer space.
You've kind of already addressed this in that answer, but with IOV-4001, where do you imagine TILs eventually fitting into the treatment paradigm, either with advanced melanoma or potentially other solid tumors? Is this a combination therapy? Does it replace other lines of therapy? Where do you see TILs kind of getting here at the end game with the treatment regimen?
Yeah, we at Iovance feel that TIL is really—this is the next—remember, 90% of cancer deaths in this country are from solid tumors. So as good as the CAR-Ts are for liquid, we really needed something; patients, practitioners needed something for solid tumors. I think this is the next—this is the next chapter in immunotherapy for solid tumors. And I think it starts with our melanoma indication with Amtagvi. But we are now—and that's in the second- and third-line space. Remember, Amtagvi is the first and only approved FDA-approved cell therapy product for unresectable or metastatic melanoma. And it is the only approved agent in the second line for these patients with metastatic melanoma that is progressed beyond the first line. So when we see TIL moving forward, I think we see potential combinatorial strategies and actually moving to an earlier indication.
So we're looking at that now with our confirmatory trial, TILVANCE-301, which looks at TIL versus TIL with Pembro versus Pembro alone with crossover. And we're seeing some, and that was developed with two primary endpoints of ORR and PFS. And again, if we look at our previously disclosed basket trial that looked at patients who were immune checkpoint naïve, who received TIL and checkpoint, we saw response rates that more than doubled what we saw in the second line space. So we're very excited to see some output of that TILVANCE-301, and this continues to accrue globally.
Fantastic. Thank you. Yeah, that was something I definitely wanted to bring up. The TILVANCE program, excuse me, trial is also very exciting, and we're excited to see that readout soon. I would be a little remiss though if we didn't talk a little bit about non-small cell lung cancer. We had a clinical trial that was put on hold but recently released. I was wondering if you could give our audience a little bit of an update on that trial and how you foresee that progressing over, again, the next six, 12 months, etc.
Yeah, thank you for the question. I think, obviously, the clinical hold has delayed the initial enrollment plan, but now that it was just removed, we are, of course, proactively re-engaging with all our participating sites to reactivate enrollment. As we just recently communicated, we are planning to complete it in 2025. As we will progress with the enrollment, we will be certainly more specific on the timing in the future. But we are very excited about the opportunity with, you know, NSCLC indication with IOV-LUN-202 clinical trial. So all stimuli on this program.
Yeah, yeah, yeah. And backtracking a little bit too, as we bring up non-small cell lung cancer, we also have cervical in the pipeline as well. I was wondering if, you know, talking about later generation TILs or the current pipeline, what goes into the calculus to deciding which indications to pursue or not pursue given such an active pipeline as well as an approved product already on the market?
Yeah, that's a it should be almost a question to Peter, but I'm going to try to answer it because, again, this is important to us. I think we're looking at a few different factors when we think about the selection of current or future solid tumor indications to be evaluated. I mean, we, of course, look at the unmet need and the lack of standard of care. We look at the high mutational load that's important to us. We, of course, look at existing clinical data from academic centers that we can leverage and understand each indication and where TIL could benefit the most. And I think, of course, potential improvement in ORR, durability versus the current standard of care and the available care is critical to us. So that's how we are looking. But Peter, feel free to chime in and add anything if you want.
No, yeah, I think you hit it all, Jean-Marc. We're looking to really address unmet need and elevate what is effective and what is available to these patients with these diseases that, again, number. If you look at the endometrial space, we're seeing disease incidence that's, you know, more than 10 times that we see in other gynecological malignancies. So we feel there's a real potential impact.
For the sake of time, we have to move on a little bit. Another thing I would really like to touch on and something we get a lot of inbound interest on is talking about ex-U.S. markets, right? Currently, we have the approval in the United States. I was wondering if we could just give another high-level overview of the current efforts into looking at markets outside of the U.S. for TIL therapy.
Yeah, one of the things we communicated recently, I mean, and we're really pleased about our progress ex-U.S. I mean, the EMA has aligned around C-144-01 in our existing trial to serve as the basis for the submission, which is on track for the first half of this year. So again, another very good news and good milestone for us. We, of course, also engage, and we have said that, with health authorities in Canada and in the U.K. with a planned submission there, you know, for later on in the year. So sites in these territories have already participated in our clinical trials, and of course, are excited about the potential for approval. So again, moving nicely on the ex-U.S. strategy.
And kind of circling back to some of our initial comments and conversation about, you know, the process of getting approved in the United States, obviously, you're probably more than prepared for some of these regulatory agencies and what may come up there. But again, I was wondering if you talk about if you run into any of similar roadblocks or hurdles when approaching these agencies about getting TILs approved in different regional markets?
You know, we will obviously leverage our learning from the U.S. regulatory pathway, all the discussion we had with the FDA, and as much as possible for EMA and also U.K. and Canada. But, you know, we are definitely interested to reach those markets because there is a large unmet need. We've talked about that. So we are, you know, preparing for, again, the submission in EMA first half of this year, so meaning we have the potential to begin launch in Europe in 2025 with a focus on countries where there is a prevalence of advanced melanoma and also precedent for cell therapy introduction with this market. So we're talking about Germany, we're talking about France, and again, to mention, of course, U.K. as well as Australia and Canada. So there is clearly a significant opportunity for us in those markets.
Again, now that we have Amtagvi available, we, of course, are focusing on the successful launch in the U.S., but in parallel, we are definitely moving forward with the ex-U.S. strategy.
Fantastic. I think it's obvious to myself and our audience, there's a lot going on. One of the final questions I'd like to ask you two is, you know, you've always been very strategic and very smart with your capital resources. I was wondering if you could maybe, again, address with our audience where you are with capital and how you foresee the next 12-24 months.
Yeah, so I think, you know, it's important for us, as you say, we have always been very mindful about our cash and our expenses and how we allocate the proper, you know, resources to the different clinical programs, but also the manufacturing expansion and getting ready for commercialization. So we maintain our guidance, you know, for cash burn of $320-$340 this year. We maintain our guidance to say that with conservative revenue coming from Amtagvi and Proleukin, we have enough cash in hand until early 2025. So, you know, again, very mindful about how we allocate our resources. And for the audience and, you know, what's coming, I think, of course, we'll talk more about the launch update throughout the year. This is, again, a clear focus for us, and we remain, you know, high importance from all the organizations to deliver on a successful launch.
We will update, you know, the clinical data in frontline melanoma, as we said, at a medical meeting later this year. So something, again, to be looking for. As we just mentioned, I think ex-U.S., we'll get a three-process progress and MA submission first half of this year. So a lot happening in the coming weeks for Iovance, and, you know, everybody should be excited as we are.
Absolutely. In our final moments of this chat, I want to give you, Jean-Marc, or Peter, an opportunity if there was anything else that we didn't cover in this conversation, either current things going on in the pipeline or, as Jean-Marc kind of highlighted, some upcoming milestones, anything else you'd like to underscore with our audience before we sign off?
Yeah, I think I'm just saying.
No, I'll just say.
Oh, good.
Go ahead, Jean-Marc.
No, good.
I'll just say at this point, we're very excited. The launch has exceeded our expectation. We continue to march towards our goal of 50 centers onboarded by the end of May, and we're very much on track there. And we really believe this is kind of the tip of the iceberg. So we're very excited to move to that goal. And I think this is a very exciting time for cell therapy and for Iovance.
Yeah, and I will have exactly said the same thing. You can feel the excitement internally and externally. All our ATCs are, you know, super excited to bring onboard patients and add new patients. So, you know, for us, it's about delivering on the successful launch for sure.
Yep, great. Fantastic. Sounds like everything is going excellently. I just want to take a moment and thank you both for joining us today. I really appreciate the time to discuss Iovance with us. Thank you again.
Thank you, Matt.