Iovance Biotherapeutics, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Yes. My name is Brian Gastman. As mentioned, I am the EVP of Translational Medicine and Research at Iovance Biotherapeutics. On behalf of myself and the company, we'd like to thank H.C. Wainwright and their teams for allowing us to speak today. As you can see, there's a lot of detail here related to forward-looking statements, which as you can read in the slide. The key message here is that Iovance has taken TIL therapy from science and academia into commercial reality. We're using this as a platform to bring these type of treatments across multiple solid tumors. As a brief overview, we are the global leader in innovating, developing, and delivering TIL therapy for cancer patients. As you can see, we have two therapies that are approved. One is Amtagvi, which is our flagship TIL therapy.

The other is PROLEUKIN, which is also called interleukin-2, mostly supports Amtagvi but has other uses too. Both are commercialized for our company. As you can see, we've treated over 2,000 patients, both clinically and commercially, which is by far the largest ever. At the middle, there's some information about market access. I'm going to get more into that as we proceed into this talk. I want to focus a little bit on the right side, which is our recent company financial disclosure. We had a record quarter in Q2 with nearly $100 million in revenue. Our margin is now 56%, which is the best ever, and we have cash runway over $300 million, which is enough to take us into mid-2028. Moreover, allowed us to now announce that we have a clear line of sight to profitability.

This slide describes how TIL therapy is made for patients. Before I mention that, though, you should know that I spent 18 years as a surgeon, physician, scientist, and trialist with a heavy focus on TIL physiology and how to overcome tumor immune evasion. Joining Iovance was an opportunity to see that realized in a form to actually treat the same patients that I was struggling with in the clinic. What you should know is that TIL is a one-time therapy made from the patients for that patient. We take the tumor from the patient through a small surgery. The immune cells that are in that tumor are very specific in that patient and used to be revitalized and expanded into the billions and given back with a preparatory method right to the same patient that we took it from.

These are the same therapies that have been around for a number of years, which Iovance then came along and scaled, and now are able to develop this, as I mentioned, as a true platform to help patients across solid tumors. We do this in our central manufacturing hub in Philadelphia called ICTC or Iovance Cell Therapy Center. As you can see, this allows us to bring in specimens, tumor specimens, as mentioned, from around the world and allow us to send the same base material in a cryopreserved form as far as the Far East, all through Europe, Asia, and certainly throughout North America and beyond. This facility supports both clinical and commercial supply. Currently, it is modular with a capacity of over 5,000 patients. The main point is that this manufacturing is not just for operational capabilities.

It is a strategic asset that supports supply control, margin expansion, and operating leverage as our volume continues to grow. Again, with the theme of being a platform, the same way we make melanoma TIL therapy, we can bring that to other tumors as well, especially large indications like non-small cell lung cancer, which I will discuss a little bit later, as well as sarcoma, soft tissue in particular, as well as endometrial cancer. In some ways, this is a de-risked platform because the cell therapists that we work with are the same across all cancer types. Many times it is the same surgeons that we are working with and in occasion, the same medical oncologist. This helps us to relaunch this drug, right now in clinical trials, but eventually commercially for all these other indications. Focusing on melanoma, there are over 8,000 melanoma deaths a year in the United States.

That is a very large unmet need. Really those patients heretofore, until we were approved, had nothing in the label in terms of refractory disease to frontline therapy, where so much success has been seen. Worldwide, you could see that number balloons to 22,000, but we are now working on a way to bring this even earlier to frontline disease, and you could see the number exponentially gets even bigger. This is a very large market opportunity alone just within melanoma, an area that we are getting better and better at as we speak. These data that I am showing you here is the basis of the trial that led to our FDA approval as well as our approvals in Canada and in Australia. As you can see, the overall response rate as well as the five-year overall survival is unprecedented in this highly refractory population.

What is really key here is in that upper right-hand corner. You can see the tail of durability. You only usually see this in immune checkpoint inhibitors in the front line. This is literally as Kate Keating used the word unprecedented, but it really is unprecedented. There is no other drug that I know of in this area, in this level of disease that has this type of durability. As you can see, we measured it finally at five years in terms of its median of over three years. When you run a trial like that, many say, "Well, maybe that is only in a controlled setting." We then went to four major centers that were mature in their ability to give TIL therapy, and we looked at their results up to that point a few months ago.

We found pleasantly surprisingly the response rates were even higher at 44%. This was driven mainly by the second-line population, which is a true on-label population with over 50% response rates. This is key because we believe as we take the same patient but get them into the true second line, we will see these kind of results throughout the U.S. and beyond. There are other measures we can do to get these numbers even higher. Without having to do any modification, any additional scientific evaluation, just working on operational excellence from the patients themselves to the doctors to our manufacturing, we believe that this is not even the ceiling of where we can go. Our Authorized Treatment Center or ATC footprint is quite large. As you can see, we are highly concentrated where the patients are.

This is key because we want to maximize patient access. Patients don't want to necessarily travel far. Their doctors don't want to send their patients far from their home bases either. Thus, you can see the strategy here. We have over 95 centers already, mostly all the well-known centers you can think of. In addition, around one-third of these are in the community, and that is growing as well. We expect by the end of the year to hit 110, and we will go beyond in the following years. From a market access point, on the right you can see that already what I just showed you in a footprint is that over 95% of patients are within a 200-mile driving distance in continental U.S., and over 80% a 100 miles. That is also getting better as we strategically add more centers.

In addition, from a payer coverage, which is a big deal if you don't have this in terms of having a blockade to accessing our therapy, we've over 250 million lives covered in payer policies, including Medicare and commercial payers. That covers over 75% of the U.S., and these numbers continue to get better and better, really hindering any reasons why patients should not be able to get this life-preserving therapy. I mentioned earlier about the potential of going into the front line. So we actually performed our IOV-COM-202-1H trial. This trial was looking at TIL therapy plus pembrolizumab in the ICI-naive population of advanced melanoma. What's key here is that not only when you added TIL to pembrolizumab, an X plus PD-1 setup, we saw incredibly high response rates in the mid-60s. But that CR rate, I hate to use the word again, but it's unprecedented.

That is a very high CR rate of 30% at the time that this was analyzed. Dr. Rosenberg and the NCI show that if you get a CR with TIL therapy in the front line, at 10 years, 96% of those patients were alive, and that included from car accidents or what have you. It's a tremendous goal to hit those kind of numbers. From an X plus PD-1 perspective, I would argue this is some of the best results you'll ever see. On the right, you can see patient-level data. These data are even more mature than what I'm showing you here. In ESMO, there'll be an oral presentation on these data, which you can also see on iovance.com. This is also the experimental arm essentially of our phase III international confirmatory trial, also called TILVANCE-301. That trial is running as we speak.

It's well underway. It's international. It's at many dozens of centers as we speak. The goal of that trial is multifold. One is to confirm our second-line accelerated approval. Secondly is to also get accelerated and ultimately full approval in the front line as well. Here I'm showing you our strong and arguably the largest and most robust pipeline in all of TIL therapy oncology. We have both our platform of our standard TIL going into various indications, as well as our genetically modified and other next-generation programs. You should know this is just a snapshot of some of what we are doing. Part of what I do is run early phase development in the company, and we are developing next-generation therapies that aren't listed here that I'm very excited to eventually be able to bring to you.

But for now, let's focus on what I have on the slide. Let me start with bringing the same TIL therapy I mentioned earlier to non-small cell lung cancer, specifically non-squamous type, wild type for EGFR, ROS, and ALK, which is actually the most common form of lung cancer. You could see the unmet need is huge. It's much larger than melanoma, at least 7X larger in terms of deaths in the U.S. alone. We have shown multiple times through public pathways a stable nearly 26% response rate as recently as last year. What's key was when we presented that data with over 2 years of follow-up, the median duration of response was still not reached. This is very akin to what we saw with melanoma. We are imminently finishing this trial very soon. I mean, really very soon.