Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Perfect. Well, thanks so much to everybody who's tuning in here. I'm Joe Catanzaro. I'm one of Piper's biotech analyst. It's my pleasure to welcome Iovance and their President and CEO, Maria Fardis. Maria, thanks so much for making the time here.

I guess if we could just jump straight into it and, obviously, maybe start with non-small cell lung cancer. So we recently got some details around the Phase II IOV-LUN-202 trial design. I guess, first, walk us through that trial design and, specifically, the thought process that went into the type of patients that you want to enroll into those cohorts given sort of the emphasis you had put into the thought process around designing this trial.

Yes, absolutely. Thank you so much, Joe, for the invitation. Happy to talk to the IOV-LUN-202 study design. We really thought about a study design that would allow us to have the earliest possible patient population that we can treat, and yet we wanted these patients to be unmet medical need. We have seen the data, obviously, from the Moffitt study, and we know that PD-L1 low expression level can yield a durable response. We had also noticed the same phenomena in our melanoma study, where the patients with known PD-L1 expression levels by TPS score of that whole group, approximately half of them were, in fact, responders when you have a low TPS score. And that was encouraging to think that while this patient population is quite an unmet medical need from a PD-1 therapeutic perspective, they are irrelevant from a TIL response perspective. In other words, the patients quickly progressed through their PD-1 -- their anti-PD-1 therapeutic, but they can't respond to TIL. In consideration of that, we thought that the patient population that we could target could be divided to 2 groups by PD-L1 expression, and we chose the very low patient population and the higher by 1%, the division line. We also decided that we are going to de-risk this study by having a Simon 2-stage design, where if we don't see a response that we are interested in, in one of the cohorts, we can discontinue them. If the response is acceptable, we have the opportunity to possibly combine the cohort. So that's how we thought about the design aspect of the LUN-202 study.

So there have been a lot of speculation around a potential focus on the mutant EGFR population. I think some of that speculation had come from the Moffitt data where they had shown a response in a patient. So why didn't that patient population makes sense from a perspective of this Phase II trial design?

Absolutely. We did, in fact, pay attention to that data, and we are highly encouraged to see that these patients do respond. However, the patients with actionable mutations are typically treated with TKIs as their first line, sometimes up to 3 rounds of TKIs. And subsequent to that, they are treated with chemo doublet plus/minus bevacizumab and sometimes with atezo combined. So that particular second-line patient population is not an unmet need. And in other words, if you wanted to go to unmet need in that population, we would have to be in third line or later. And we were just concerned -- as I noted earlier, we were concerned that we wanted to have patients that have some degree of health left in them so they have life expectancy to participate in this study. So we excluded those patients because we didn't think that the second line would be unmet need.

This emphasis on pushing TILs into the -- as early as possible in the treatment paradigm, is there any learnings you've found over your entire clinical around TIL generation from different patient populations based on the number of pretreatments? And is there any indication that those with less heavily pretreated disease tend to generate a TIL product that is just more favorable, which can in turn lead to better clinical outcomes?

The decision on trying to go to early line is not based on a manufacturing experience or a notice of the phenotype or the profile of TIL product being different. It's more of a clinical observation that when the patients become heavily pretreated subsequent to multiple lines of therapy, particularly immunotherapy, that they're very difficult to turn around with yet another round of immunotherapy. From a manufacturing perspective, our manufacturing success rate has been well above 90%. This is a collective experience over the last few years, as a matter of fact. And we don't see a particularly significant difference between patients that are early line or late line from a manufacturing perspective. By the way, we also don't see a significant difference from an indication perspective as well, and we have published that data.

So we've touched on Cohort 1 and 2, but there's also a couple of other cohorts. I guess, first, maybe Cohort 3, can you just describe what you're trying to do there and what kind of information you're trying to glean from that cohort?

Absolutely. We are offering a core biopsy, which is a smaller amount of tumor to be collected in case of Cohort 3. We intend to grow the TIL through a Gen 3 manufacturing process, which is a shorter manufacturing process of Iovance. And the reason we chose this, the patient population is PD-L1 negative, so the very low patient population. And the reason we did that is we wanted to have a nice comparator with other cohorts of this study, so a clean patient population. And in general, from a strategic perspective, we are optimizing our administration of TIL, trying to turn it into a more patient-friendly process, so the smaller mass of tumor is a step in that direction.

So was the decision to include a cohort -- this cohort in any way and form from your prior experience in lung cancer from the COM-202 trial? And I'm asking specifically from the standpoint of finding patients who have easily accessible -- easily resectable lesions. Maybe it's more difficult in lung cancer than it is so in melanoma or even cervical.

That's an excellent point. There certainly has been a presumption that it may be harder to sort of resect a lung tumor compared to a melanoma tumor. Our surgeons tell us that particularly in the patient population, we are dealing with, which are the metastatic patient population, that they're able to resect sufficient tumor in the non-small cell setting. So for the patient population we are dealing with, we haven't seen a significant difference. But in general, our approach to core biopsy is toward, as you noted, collecting a smaller amount of tumor for various indications. Even in melanoma, if we can get away with 3 core biopsies, that's a great outcome from my perspective. So we are trying to make this a more easier-to-administer regimen.

So you mentioned that Cohorts 1 and 2 are using a Simon 2-stage design, which is something you guys have kind of utilized quite frequently in some of your other trials. And if we think back to some of those other trials, the trigger point is largely around a 10- to 20-patient cohort size before you decide to upsize. Does that also trigger a potential discussion with the FDA around, first, do we combine these cohorts into a single cohort? And then subsequent to that, what do we need to show in a registrational cohort out of this trial?

Yes. I think the way you're thinking about it is very appropriate that, at some point, when you have enough patients in the 2 cohorts, one can make a decision. I just don't know because we haven't obviously started patient dosing. I just don't know how the rate of enrollment in these cohorts would be and whether they're going to be done sort of one-to-one. They may not be. So one may be further along than the other one. Presumably, if a situation arises where we have approximately the same number of patients in the 2 cohorts, we can take a step, as you are describing, to sort of start talking to FDA. But it requires that the 2 cohorts have approximately the same number of patients so we can actually compare them appropriately. I think it's a little early for me to be able to tell you what's going to happen. But certainly, look forward to being able to update The Street if we have additional information.

So there's also Cohort 4 within this trial, and I received a question earlier this week on why -- on whether you've done this before. So this is the retreatment. And I know there is one similar cohort in the melanoma trial, but your experience there, I think, had been -- it's a little difficult to get a patient who has previously received TILs and progressed to recommit to the TIL process once again. So is this purely just an exploratory cohort to just offer it to the patients if they so choose to undergo the procedure again?

It actually is a result of the request from the patients and the physicians. Almost all of them require or request that they would have the opportunity -- if they wanted to come back and get retreated, that they would have the opportunity to do so. So we have created a platform in every study. In fact, all of our studies do have a cohort for retreatment should the patients decide to do that. In melanoma, we initially started with a little bit of a strategic thinking around could we resect a tumor that would have a different TIL profile than the original tumor. And would that give a different response? Initially, that's how we started thinking about it. But it has become more of patients would like to have access to retreatment, and therefore, we want to make sure that we have a platform where we can offer that to them.

Okay. Okay. Got it. So last question with regards to lung cancer, which I'm sure you get frequently, is, what are expectations around presenting data from the lung cohorts of COM-202 and being able to see what kind of data do you have that you're using to support the initiation of the LUN-202 trial?

Yes. So for -- in terms of data flow, we certainly don't commit upfront to data flow. Typically, our strategy has been that if we have submitted our data, we got accepted into a conference, then we disclose that we did get accepted to the conference. We certainly did pay attention to our COM-202. There was lessons learned from that study in terms of the patient population. In COM-202, we have 2 cohorts of patients. One is checkpoint naive, and we are combining TIL plus KEYTRUDA in that patient population. That's Cohort 3a. And Cohort 3b is a relapsed/refractory patient population, which is expectedly post checkpoint, and many of them are third or fourth line or later. And that's been just our general observation in our TIL program. What we learned is that early-line patients are very difficult to find, particularly in a COVID era where patients may be more apprehensive to travel. And the late-line patients, specifically in the lung setting, don't always survive to give us a data point. And we have seen this before in our head and neck program, for example, as well. So in fact, we did learn something just by observation of the cohorts and the patient population that we use for LUN-202. We have chosen a patient population which is sort of in between for LUN-202. We have chosen a second-line patient population.

So it sounds like there's 2 things. It's, first, having a data set that you internally feel is ready to present and then subsequently finding the venue to present those data from COM-202 lung cohorts.

That's probably a statement, yes. Thank you.

Okay. I wish -- I probably had something else I could ask there, but we'll move on to head and neck cancer and the data you recently presented at SITC with regards to the pembrolizumab combination there. The response rate we've seen there, I think it very clearly indicates that this combination is well outperforming pembrolizumab monotherapy in this recurrent head and neck setting. But I guess, how should we think about next steps in terms of this data set evolving and maturing and what you want to see out of that to get comfortable that, okay, this combination is, in fact, providing a durable long-term clinical benefit over pembrolizumab monotherapy and even TIL monotherapy?

Yes, absolutely. It is very exciting to see 9 patients' worth of data, but we certainly acknowledge that it's early days and with a short follow-up. So we certainly want additional patients and longer follow-up before we can decide what exactly is the role of TIL in combination with KEYTRUDA in the patient population. But it's certainly exciting given that in post-chemo patients, anti-PD-1 typically would have around a response rate of 16% or so. So we are excited and encouraged with what we see at the moment, but we'll need to continue with additional patients to make sure that the data is accurate and representative.