Great. Thanks, everyone, for being here. My name is Yanan Zhu, and I'm one of the [biotech analyst] here at Wells Fargo. It is our great privilege to have the management team of Iovance Biotherapeutics here with us for a fireside chat. With me on the stage are Corleen Roche , CFO, and Brian Gastman, EVP Medical Affairs. Thank you for being here.
Thank you for having us.
Thank you.
Great, great. For the opening question, I wanted to ask Corleen because Corleen , you recently joined Iovance last month on the new role. You have a long track record as the CFO at many companies that our investors know very well, like CG Oncology, Biogen, Pfizer, and you have overseen many commercial launches. What drew you to Iovance at this juncture of the company's journey?
Yeah, I'm very excited to be here and to talk to you about all of the good things that drew me to Iovance . Number one, we can't forget the product is good. It works. It's on the market. It's helping people. That's the most important thing. We can manufacture in an efficient way. You might hear a little later on that we'll have some continuous improvement on that, but it's in our control, and we're doing it well, and we're doing it timely. That's important. The product is getting reimbursed. These are all great things. People sometimes ask me, you know the stock dropped. Why did the stock drop? Because we maybe made some incorrect assumptions as we guided into a brand new market, right? We're resetting that now. We have learnings, and we re-guided $250 million-$300 million this year, which is reasonable.
We did the right next thing, which is right-size the organization, right? We're making sure that we have the financial discipline to make sure that the business is profitable as soon as possible. These are all tremendous things. I'm very, very excited about Iovance 's future.
Great. If I may ask a follow-up on guidance, obviously, the new revised guidance for this year is $250 million- $300 million. Can you talk about the key initiatives that will get the company to deliver in that range this year and the next set of growth drivers that will get revenue beyond $300 million?
Yeah, absolutely. For the $250 million- $300 million , first I want to mention that we saw quarter-over-quarter growth in Q2 of 24%. We're already ramping. I think that we have a lot of external-facing initiatives in the current authorized treatment centers. We're also adding authorized treatment centers. More importantly, we are adding large community centers. We're trying to bring the product to the patient and make it easy for that to happen. Instead of, you know, they're in their own ecosystem within the hospital and they're moving from product to product, they can just move to Amtagvi after another product more easily than moving to another center. We have those learnings. We also signed a contract with Biologics by McKesson, which is a specialty pharmacy that gives providers another option.
Should they not want to pay directly for the product and have the reimbursement, they can buy it through a specialty pharmacy. Right? Say cash flow is an issue. We just want to make the product as accessible as possible. All of these initiatives should drive further growth in getting product to the patients that are there.
Great. Thanks for that cover. I wanted to maybe ask a question on kind of dissecting what happened so far in terms of the launch at a patient level, such as, you know, because we know things like insurance clearance, scheduling difficulties or ease, turnaround time for manufacturing, success rate for manufacturing, those, all the logistics go into whether that turns into revenue or, you know, otherwise. Could you talk about those parameters? So far, what have you done well and what needs improvement?
Sure. I'll take that. Thank you. The journey of the patient from ordering to infusion includes things like financial clearance. I could start with that. First of all, that has improved significantly. Our average time is around three weeks, but we've seen it even earlier than that. What we're seeing happening also is a parallel action item. For example, in the past, everything was in series. You waited for certain clearances, then you did the scheduled surgery and then looked for slots in our system. Currently, we're really constricting that down because centers are now more comfortable with us, we're more comfortable with them, and we're able to identify surgical dates and slot dates as well at the same time as we're getting financial clearance. What we've done is seen to constrict.
We've done this in a way to constrict down the amount of time it takes from an order to the actual infusion, which is going to help not only for the patient journey, but from a financial perspective from our company. I would add that the turnaround time going from 34 days to 33 days, it may sound like a little bit, but it's pointing in the right direction. It shows the consistency of what we're doing in our manufacturing. Also, sometimes even a day or two makes a difference in terms of a whole week of when you would start lymphoid depletion and actually treating the patients. I would add one more item to all this that prior to even ordering Amtagvi is the referral for it. That's something we've done a lot of work in, and specifically, we want better patients.
Remember, the vast majority of melanoma patients are good Amtagvi patients. You just have to catch them at the right point in their treatment journey. By doing it, by getting the message out there that if you can bring them in earlier, it's easier on everybody, on their system, on our system. Ultimately, what we've shown with some of the real-world evidence is that we're going to get better outcomes.
Right. Thank you for touching on the point of, you know, an earlier patient is easier for everything in the whole process, including the manufacturing success rate. What progress are you making in terms of catching earlier and earlier patients? You did mention this real-world, and I think you announced some real-world data with very good, even better than clinical trial results. Can you talk about the catching earlier patients and talk about that real-world analysis you did?
Sure. So there's multiple areas that we are focusing in on. We early on got NCCN adoption. Remember, we're the only drug that has in its label refractory melanoma. We are designed, even in those guidelines, to be a true second-line therapy. We are trying to get that message out even more than just letting the guidelines speak for themselves, but pointing referring physicians to those guidelines and reminding them that's really where we should be positioned for their patients. The question then is, why would they want to do that? First of all, the alternatives don't work. That's number one. Number two, when they overly use those non-working alternatives, as the physicians tell me, they quote-unquote "beat up the patients." When they get to the authorized treatment centers, they could be too sick. Their immune systems could be altered to a point where it's harder to manufacture.
On all those levels, it makes it much easier. In the end, we knew from data from the NCI, from even our own studies in the front line, that the earlier these are adopted, the better the results are. What we did in there is we actually worked with some of our centers randomly, but we wanted a nice biopsy across the U.S., different types of centers. We asked them, give us some data, and let's do a first-ever real-world evidence of commercial Amtagvi. What we found was that, and this was unbiased, the results were better than our trial overall, but it was even better, over 60% response rates, which is incredibly high in the refractory position if you only had one or two lines of previous therapy.
If you think about how good front-line therapy is in melanoma, and you add in a 60% response rate if you give us in that sequence, that's a huge opportunity to cure a lot of patients. I mean, you know, they used to say that melanoma puts the fear of cancer in cancer. I think we're moving into an era, especially with our drug, that we can move beyond that, which is our hope, of course.
Great, great. I wanted to touch on something about referral from the community, maybe leading into some initiatives that you have right now that is to reach out to large community networks and actually turn them directly into ATCs rather than referring patients to ATCs. Can you talk about the referral pattern so far and the opportunity and perhaps why didn't you target large networks in the community before and you're targeting them now?
Sure. First of all, you have to remember that the data really showed that about 1/3 of all melanoma were being treated in the exact authorized treatment centers that we were targeting. The centers that we targeted had the expertise from the clinical trials, our own and others. They had the expertise in financial clearance. These were the top CAR T centers in the United States. They were the obvious low-lying fruit, and that's why we went after them. Based on the data at the time, it made sense that that would more than fill up our slots that we had. What we came to realize over time was that the vast majority of the patients that they're treating with Amtagvi were referred in.
If you look deeper into that, you find that there's these large community practices that have acutely grown into these enormous entities that didn't exist previously. We mentioned this before, that you can Google some of them and how many patients in the United States are now being treated by them. That wasn't the case earlier. What's key here isn't just getting them to refer to the appropriate authorized treatment center. Even if they're willing to do that, there's many steps that go through it. Will they force their centers to try recycling PD-1 therapies or other therapies that ultimately won't work before the inevitable, and thus quote-unquote "beating up the patients" with all these drugs that we knew probably wouldn't work anyway, versus trying to keep the patient in the same ecosystem where it's very simple? They failed drug A, go to drug B.
Of course, it would be the obvious drug B, especially if it's already in their formulary or already within their own institution. It not only moves the patient to the obvious next choice, it does so in the most efficient manner right where the patients are being treated. We think there's a huge opportunity. 10 years ago, probably this wouldn't have been a smart move. Today, these are the realities on the ground, and we have to do it.
Got it. Yeah, definitely looking forward to an update on the progress for that outreach. Another component of the revenue is obviously IO2. Can we talk about IO2 dynamics? What are the potential dynamics in the next quarter or two? It was lumpy up to date. We have highs, and we have lows. When will this become less lumpy and more reflecting of the ongoing use of Amtagvi?
Yes, lumpy is a term. It's a technical term that we use for the IO2 sales. Let's back up and say, okay, what happened, right? In 2024, these three distributors came on board. They stepped in, and their repurchasing patterns didn't start for a little while. We've seen two of them come back and start to repurchase, and we expect that to even out over time. Let's make sure that we talk about the, I'll call it the three buckets of IO2 use. One is with Amtagvi, right? The other one is we sell to manufacturers for their product use, for use in their manufacturing. There's also a commercial use for Proleukin. That can also throw it off a little bit. What we're seeing, I believe, is just the stock in and drawdown of the three distributors.
That should, we're hoping, equal out by the end of the year and get a little bit smoother. I can't promise that won't happen again. It depends on when they want to buy the product and when they want to store it and when they don't.
Right. Directionally, was the last quarter a relatively abnormally low quarter, and it should go up or anything?
The first quarter was low, and then we started to see a little bit of restocking. I think that's why I'm hopeful that by the end of the year, those reorder patterns should become more potentially in line with Amtagvi demand.
Got it, got it. Maybe a longer term, again, sales aspiration question. I think the company has noted there is potential for Amtagvi to reach $1 billion in the U.S. Can you talk about what is needed to get to that sales level?
Yeah, I mean, absolutely. That's the opportunity that I came here for. All of the initiatives on the commercial side that we talked about, the large community practice, I personally would probably boil that down into getting the product to the patients at the right time, right? That probably entails maybe even some more initiatives on education if we can get to the patients as well as the doctors. We're using the learnings that we have seen in the treatment centers. I'll mention that our addressable patient population globally in the countries that we're looking at is about 30,000 patients per year. We're going to try to capture as many of those patients as we can because I think Amtagvi has a real shot at helping people.
Got it, got it. Let's also talk about E.U. opportunity. That's, you know, a potential growth driver. The company recently announced that you withdrew the application to the E M A. A virtual control arm may be needed for recent.
Yeah, I can kind of give the high level, and then I'll let you talk about the virtual control arm or the historical control arm. It was sort of late in discussions that we realized we needed to have this data. They would really like us to have this data. We had already filed, and there's no mechanism at that point to supplement that. We withdrew it. We're quickly working on our strategy, and it's a virtual control arm. We don't have to do any more studies. We'll resubmit.
Okay.
Yeah, and the EMA has a long history of using the virtual control arm, specifically in oncology drugs. For their approvals, you can look up the percentage. It's not insignificant. This is nothing new there. The bottom line is that, you know, we went in sort of like we do the FDA as we saw with CAR T, but we really aren't a CAR T. We're the first ever cell therapy in a solid tumor, which is 90% of all cancer deaths. It's a completely different world, a different mindset, different rapporteurs. They have to look at something like this. While there is some overlap with CAR T, it's not the same animal, and it was clear and obvious. They need that to really understand what we're explaining to them to the point that we can make this basically at the same level that we have in the United States.
Got it. Looking forward to updates on that front. We talked about the revenues, the opportunities, and let's talk about controlling cost.
Yeah.
Another important initiative with the company. Can you talk about your efforts on that front, especially on gross margin? I think we should.
Yeah, absolutely. Look, we're committed to further streamlining and optimizing our business. How are we doing that? We did the restructuring in Q2. That was a big deal. We right-sized the company for the revenue ramp that we're actually seeing, right? That includes capacity in the plant. We'll have enough capacity to ramp, but you know, there was probably a little bit more in there that we could do. That restructuring impacted OpEx. We said conservatively at least $100 million savings over four quarters. That doesn't include the cost that we saved in the cost of sales. We didn't guide that. You'll see that will impact the margins. That also extends our cash runway into 4Q of next year. What I can say is one of my goals as a CFO is to ensure that we have consistent financial discipline. Where are we putting the resources?
Let's make sure that it is optimized from a resource allocation perspective. We're investing where we need to, right? We're being, I would say, prudent about all of our investments. Does that make sense?
Yeah. Putting a more specific number out there, your 1Q non-GAAP gross margin was 31%. Talk about that number and where do you think it goes from here. What are the most important levers you can pull to improve that margin?
Absolutely. I think that was Q2 non-GAAP.
On Q2, sorry.
Yeah, 31%. Look, improved capacity utilization. We've done that as far as the restructuring that we did. We right-sized that capacity. As we grow volumes, any of that sunk cost, fixed cost will be absorbed. We have also other initiatives ongoing that will make the process more efficient as well as saving costs. I don't want to go through the name of all of them, but it's a focus. I can promise you that. Every efficiency that we have in the plant is going to reduce margins. You'll start to see even more of a separation as the volumes absorb the fixed costs.
Got it. Is it okay to ask when the company might hit break-even?
We haven't guided that, but I think we're going to do that as soon as possible. That's the goal of all of these initiatives, right? We reset the revenue. We're looking at the cost base to really get to that point.
Got it. You talked about cash runway. What measures can the company potentially take to further shore up the balance sheet?
Yeah, I mean, as the CFO, that's what I think about a lot. You know, what can we do to strengthen the balance sheet? There are a lot of things that we can do. We're looking at all of them, of course, and considering them, including non-diluted at this point. There are many different ways to do that that are available to us, I would say. As we continue to forecast and look at our position, we may look at one or multiple of those ways of shoring up the balance sheet.
Great. Let's talk about the pipeline. I think a lot of investors are looking forward to the non-small cell lung cancer update later this year. Maybe start us off by talking about the trial that you will report and the venue, the timing, and the patient number. Thanks.
Sure. You're referring to our LUN-202 trial, which is a true second-line TIL trial after chemo- IO, or essentially the major mutation wild type, EGFR wild type non-small cell lung cancer, which is a huge scourge in the United States and around the world. You know, 150,000- 180,000 deaths a year from lung cancer. A lot of it's from this population. The magnitude is 10x- 15x larger than we're dealing with in melanoma. The unmet need is huge. They were reset in terms of their front-line therapy some years ago. Unfortunately, after five years, over 80% of all those patients will have died. Not just forget durability response. The need in the second line is huge. Yet we've seen almost no movement in that area at all, other than potentially what we're about to report.
We had reported some early data a couple of years ago, and we had committed, and we still are committed to having a much larger data set by the end of the year. While it may not be our final number of patients, it should be large enough that when we do add some more patients to it, that roughly will be the data that we would ultimately present in our final fashion and use as a registrational package, because that's what this is. This is a registrational trial. At current, we are planning on doing this likely as a press release, in part because our company is committed through multiple discussions with the FDA to use external review, independent review. That's expensive. It's timely.
We can only do it so often, and it doesn't always, you know, just happen to meet up exactly when the deadline of the best conference is. As we allow the data to mature, and I think we've discussed this before, we are very keen on the fact that ours has this incredible durability potential. We have to let patients show their durability. Otherwise, it's too early to show it. At this point, it's likely we will do it through a press release, but with the intention to also do this as a Congress presentation next year. With that, using that as our registrational trial. Our goal from a benchmark perspective is to have response rates, which would be consistent with our last reporting, to be in the 20s and have durability of at least six months.
Of course, being a living therapy, sky's the limit, but I think trying to hit that six months benchmark is very reasonable. So far, we've been very consistent that our data has always shown that we should be able to hit that mark.
Got it. Can you talk about the, you know, to put those ORRs and DORs in perspective for us, talk about the landscape for a second-line, second-line non-small cell lung cancer. I think there's recent development in the field, but what does the competitive landscape look like?
Right. The standard of care really is chemotherapy. There are combinations with other drugs, but really docetaxel is the main one. If you look at the larger space retrial, the REVEL trial, where it was used as a control arm, the median progression-free survival was three months. Terrible, right? That includes loss of stable disease, not just loss of responses. It's really awful. Yet that's the best that's out there. Most of what you may be hearing in non-small cell lung cancer is an EGFR-mutated cancer. For example, those bispecifics that are making a lot of noise are not working in the cancer in this large group of non-small cell. It's working in the EGFR-mutated population, which IO previously has failed in. That is not really disrupting what we're looking at right now.
ADCs have been long tested now in this population, and sadly for the patients, have essentially failed across the board. We don't really see a lot of competition in this population right now. There are phase I and phase II trials, which are interesting. A lot of them are me- too trials also, just to be frank. Why one didn't work and the other one will because of a different company? It's hard to believe. Of course, that's what they're touting. To me, I don't see any major addition to the field outside of what we're doing for that population.
Right. Got it. Do you expect the long duration because you do have very, very long duration for your melanoma patients, right? For lung cancer, I think one key thing is that long tail that people are looking for. What is the likelihood that the melanoma data will translate to lung cancer? Can you share some thoughts?
If you look at the SOAR plot that we showed in the fall of 2023, you would see over there what we're talking about duration-wise. Already in that early data set of this trial, 71% of patients had +6 months of duration. It's kind of like that was a fluke in just the first 20-something patients, right? That's number one. Number two is we had data, obviously, in more heavily pretreated patients, the IIIB population that was published. We have data in the front line, the IIIA. We had already done an earlier trial, a phase I trial that was published as well. All these are in peer review publications, actually, the IIIB and the earlier phase I. You can see already the signals of durability. The key here is that this is a true second-line population, which really has never been tested before.
We've always seen whether it's melanoma and now lung, the earlier you do it, the better the results. We know what it is with heavily pretreated lung. We expect to only do better. We know sort of maybe the ceiling is the front line. What I will tell you came out of the front line, though, which is really key, and it's important to know from a competitive landscape, is that most companies at best are looking for PD-L1 moderately expressed, if not highly expressed. In fact, a lot of those bispecifics require high PD-L1 expression. We found that even PD-L1 negative, completely no PD-L1, our drug works just as well. That's really important because we don't have to work around that fact because that is the most unmet need population, period. The great thing about our drug is that we can go right after that population.
I don't see any other drug doing that.
Excellent. Thank you so much. That's super helpful. Have you had interactions with the FDA recently confirming that single, you know, as you said, the LUN-202 is supposed to be the pivotal data set? It's a single-arm trial for accelerated approval based on ORR. Have you had more interactions to confirm that? What's the bar that the FDA might be looking for approval?
As you know, one of the things that Iovance has uniquely done is basically hire former leaders in the FDA , specifically experts in checkpoint inhibitors and cell therapy. Our CRO has literally hired a lot of the people that are making those decisions right now. Not only does it make the interactions more effective, but also the timing of those interactions is done with a strategy. We have a constant set of discussions with the FDA. We know when to do that, why to do that. In doing so, we have only had positive feedback. I would say that those discussions help craft what our current trial is. In fact, we had a very short hold on our trial. It was like a record, 24 hours within responding, and we were off hold, which shows you how strong our relationship was with the FDA.
More importantly, that changed our trial. Our trial is really designed with a heavy influence from the U.S. FDA already. Secondly, we know the FDA has published their designs for an accelerated approval, and we are right in the middle of that publication's details. Thirdly, what I told you earlier, which is the benchmark of six months of duration, 20% response rates. That's really what we've always been heard is the kind of benchmark the FDA is going to want to see, recognizing the incredible unmet need in that population.
Great. Thank you. Thank you. Let's touch on endometrial cancer, which is another prioritized pipeline area. You will report some data later this year as well. Talk about the setup, the significance of this tumor type that you're going after, and the bar there is. Thank you.
Yeah. I think you'll see a pattern with Iovance . IO front-line therapy type patients, solid tumor, don't have great second-line options. Melanoma, non-small cell lung cancer, endometrial is an obvious another one. That follows that pattern very nicely. We're very good at it. We're moving, as you can see, from FDA approval to a registrational trial. Our hope is that endometrial will follow the same path. We've already mentioned on a recent earnings call that we've already seen some very positive signal. Remember, this is a first- in- human. No one's ever done TIL in endometrial before. It's very exciting. The more we start seeing similarities or almost a reflection of what we saw in the other trials, it gives us a lot of confidence that we are moving in the right direction.
Bottom line is we expect to have this first-in-human type data, some type of data release by the end of the year, probably press release. I will tell you that GYN oncology type conferences are less out there. It's more likely for those kinds of cancers that we might need to do press releases or manuscripts because we want high impact. We want the right people seeing this type of data. I hope that makes sense.
Got it. What about the bar there is or the competitive landscape for that tumor type?
Chemotherapy, which basically doesn't work, is the second line. The bar is exceedingly low. It's probably similar to non-small cell lung cancer. There are a lot of chemotherapies that are out there that I could choose from. Some of this data goes back decades. It's not a really pretty picture to give you a number. I could just say it's exceedingly low. I would think that lung cancer and endometrial cancer, though, have very similar levels. It is a very deadly cancer with really no options if you fail front-line therapy. With PD-1 actively moving into the front line, you're just going to basically see the failures in the second line just being worse and worse and worse.
Got it. Got it. If the data meets your expectation or even exceeds your expectation, any plans to convert the trial into a pivotal like you did for the other indication?
I'd say it's a little premature to say that, but I would say that you can watch Iovance's playbook, and you can expect, you know, we're an animal of repetitiveness in some ways. If something works, we're going to keep doing it. I would expect, as our other trials continue to go in the right direction, that we'll probably follow some kind of pattern.
Got it. Let's also definitely touch upon the first-line melanoma. You have TILVANCE 301. This is a confirmatory study for the second-line plus melanoma, but also for accelerated approval in the first line, as I recall. How is the enrollment going? I was remembering some discussion about the placebo arm and those kinds of dynamics. When can we expect an interim, or is there an interim readout? When can we expect it?
Yeah, so just briefly, you're correct. This is a validation study to bring full approval to our current accelerated approval. It's also because it's got a dual endpoint, allows for early accelerated approval for the front- line and then ultimately full approval in the front line. Its control arm actually is pembrolizumab. There was a recent, you know, KEYNOTE-006 10-year data . The quote from the PI, the first author was, "This establishes pembrolizumab as a standard of care for advanced front-line melanoma." Guess what? Every patient on this trial gets pembrolizumab, every one of them, just like the KEYNOTE-006 10-year data . What happens is after a number of doses, there is a randomization that you continue on it versus going on to TIL. We already had phase 1A data, which was just TIL alone without pembrolizumab. Sorry, sorry.
Our data is with pembrolizumab, but there was NCI data also, which was consistent with our phase 1A data, that the ORR was in the high 60%. That's even better than, wait, that's like double what we saw in our clinical trial, right? The goal there basically is to get a readout, but it is a phase III global trial. It's definitely moving in the direction it's supposed to, but I can't give you a time commitment when we're going to present it because, again, durability is a big issue for us, especially for front- line where it's never really been fully studied. We're going to make sure that the data looks very clean and very, very acceptable before we actually present it.
Great, great. Thank you. It looks like we're out of time. I wanted to really thank the team for, you know, we went through a lot, and thanks to the team for all the insights and your time.
Thank you. Thanks for your time.
Thanks, everyone.