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

Welcome, everyone, to our next panel. My name is Ben Burnett, biotech analyst at Stifel, and I'm pleased to be joined by Madan Jagasia, SVP of Medical Affairs; and Jean-Marc Bellemin, CFO of Iovance Biotherapeutics. So thank you both for being here.

Thank you, Ben, for having us.

We will do a fireside chat. But obviously, for folks who are dialing in, please feel free to submit questions to the dashboard. I will be monitoring that or e-mail me at [email protected]. So let's just kick it off. Can you maybe just give us a quick update on Iovance where things are, just flag sort of what you think are near-term catalysts that we should be watching out for?

Yes. Thank you, Ben. Thanks for the question. I think I want to start by saying that our top priority is -- obviously remains our ongoing work to address the FDA feedback regarding the potency assays. And it's top of mind for investors. So we want to address the question to -- or being able to have a planned BLA submission ongoing. We have a continued ongoing work developing and validating our potency assays and as we disclosed recently, we have engaged with discussions with the FDA during the second half of 2021. We do anticipate the BLA submission to be as planned for the first half of 2022. And we are very confident with this time. So we also recently shared the new data to product support to pour off our TIL platform in solid tumors during SITC this past weekend. And maybe a quick overview of them. I mean first, in the non-small cell lung cancer, we think the overall results following onetime Iovance TIL administration including the durable complete response ongoing at 27-plus months are exciting in an heavily pretreated similar finding cohort. The result we shared support the potential for TIL across a range of prior therapies than in patients with diverse characteristics. Next, moving into TIL to earlier treatment setting is also a key priority in patient naive to immune checkpoint inhibitor. The combination of Iovance TIL and pembrolizumab produced encouraging efficacy with expected safety in patients with advanced melanoma and in neck cancer and cervical cancer. And this result supports our continuous effort to develop TIL combinations in earlier treatment, again in melanoma and in neck, cervical, non-small cell lung cancer and also other solid tumor cancers. And finally, I would like to also highlight actually our progress on our manufacturing capability. We recently announced the first patient receiving Iovance TIL coming from our own iCTC, our Iovance Cell Therapy Center. And to date, we have more than 500 patients that have received Iovance TIL with continuing manufacturing success rate above 90%.

Fantastic. Okay. Obviously, a lot to get into, but I want to start with just your thoughts around the CEO position. Obviously, I understand that there's a limitation to what you can comment on, but just love to hear just kind of the type of resume that you're looking for, like is it someone would the best, would be someone with a clinical R&D experience? Or is it commercial? Anything you can say on that and on the timing of it?

Yes. Thank you, Ben. I mean you're correct. There is not much we can disclose on that. But what I can say is the search of course, still ongoing and is very important. It's an important priority for our Board, obviously. And what maybe I can say is we want to find a strong candidate with cell therapy development and commercialization experience. And we don't have any guidance on timing, but this kind of search will take generally some time. But we'll definitely make an announcement when we have someone on board.

Understood. Excellent. Moving on to another topic that I think will also be difficult to talk about. Just regarding the potency assays, is there anything you can say in terms of the FDA dialogue you've had to date? And has there been any requirement at this point to change anything in your process like your clinical trial product process?

Yes. Thank you. Ben, I mean this is, of course, a very good question. And again, I know it's top of mind of many investors. So let me start first by -- what I can share with you is that we had several INDs approved by the FDA throughout the years, which include the clinical release assay we used today first. And I also want to mention that the FDA approval of assays for clinical studies is actually not required to run these studies. So this is an important thing I want to mention. But what FDA and Iovance are focusing on now is potency assays intended for release of commercial product. So we are currently working on gaining their agreement on the assays -- set of assays with them. And as with other autologous cell therapy products, variability between patients is relevant for the selection assay, but typically, it plays more role in the specification setting process. And we -- during our earnings release recently, we disclosed that we continued our ongoing work developing and validating potency assays and have engaged in discussion with the FDA during the second half of 2021 as planned. And again, we are confirming that we anticipate the BLS submission for lifileucel to be in the first half of 2022. I think this is a key, again, top priority, but this is also very important for us to reiterate that we are confident with this time. And the resolution of the potency assay for lifileucel in melanoma is also a key step towards regulatory path in other indication actuals.

Okay. Excellent. So it's interesting. I don't think I appreciated that. So there really is no kind of like official requirement in terms of release assays for clinical trial product. Is that okay?

That's the fair statement.

That's pretty standard with -- throughout the cell therapy industry?

That's pretty standard. Yes.

Yes. Okay. Excellent. I guess Iovance TIL had -- has previously talked about sort of a 3-pronged approach to addressing the FDA questions here. To what extent is this reliant on having biopsy material to kind of go back to? Or is this really about analyzing data that's already been procured just in a different way?

Yes. Good question. But just to clarify, Ben, our ongoing assay work has included a multiple -- a set of multiple assays, and we have assessed many different options as well as an interactive process with the FDA to define what we believe will be the right assay or assays to address the FDA feedback. So we await clarity from FDA on the assay or set of assets prior to using our samples. I mean for pure development purposes, we are using a mix of research samples, tumor samples we can purchase for testing as well as our clinical samples. So in summary, we are, of course, being very judicious in our use of clinical samples until we have the alignment with the FDA on the proposed assay or assays so that we have enough of our patient sample for retesting using the agreed-upon assay. But again, we do have enough sample that we did.

Fantastic. Okay. I guess, just in terms of timing, can you just kind of reiterate what you guys have said in terms of when we can learn more about your FDA interactions. And also, I'd just be curious, just how the timing of this is sort of impacting what you can do in terms of investing in the commercial launch? Like what have you done so far? And sort of where do you want to be by the time that BLA submission has in terms of sort of market launch preparedness?

Yes. So I mean it's difficult. We intend to provide an update when available. But the reality is that we don't expect us to comment on the back-and-forth conversation that are currently ongoing with the FDA. I mean we want to be as transparent as possible. But of course, we have some limitation there. And regarding the interaction may result in communication by year-end or into next year without shifting our planned solution time line, which is the important point here. So we, of course, typically provide account update as soon as possible upon receipt of any material information. And we, of course, will do the same in the future. So stay tuned for the more to come soon. Regarding your question on the investment and the melanoma preparation launch. I mean, thank you, by the way, for asking this question. We do some work there, and we are getting ready because, of course, it's coming soon. But let me address your question by talking about 2 critical aspects in our mind. I mean, the manufacturing on one side and commercial readiness on the other side. So again, first manufacturing, mentioned that we started the clinical manufacturing at iCTC to supply our clinical trials recently. And now we are advancing actually the commercial manufacturing readiness activities for Iovance TIL at iCTC. So commercial supply remain on track, pending regulatory approval, with ultimate capacity to meet the demand for up to thousands of patients in multiple indications. And I think that's a key competitive advantage for Iovance. Second, commercial. So our commercial team remains focused on customer and obviously, patient centricity to ensure a positive experience with lifileucel, I would say in 3 areas of operational excellence. First, we continue to enhance our partnership with the leading U.S. cancer centers and we are helping them to build their Iovance TIL service line capabilities to ensure that across the different teams, each authorized treatment center can administer the lifileucel treatment regimen upon FDA approval. And second, as a market access, the team continues to engage our commercial, Medicare and Medicaid payers to ensure patients have appropriate and timely access and coverage for lifileucel. And third and final, I think we mentioned that in the past, the development of our IovanceCares. This is the own cell ordering and patient support platform. It's on track for launch. And IovanceCares is designed to be customer-centric in planning, coordinating patient care throughout the lifileucel journey. We have integrated or incorporated customer feedback in the design of our IovanceCares throughout the process and it's a proprietary chain of identity, chain of course, to the system with a fully integrated patient management approach and of course, integrated approach to products. So we have a gated approach to commercial readiness and the commercial organization is well positioned to scale our efforts based on our internal milestones and time lines.

I want to ask one more sort of commercial-oriented question then move on to some of the new clinical data that you alluded to earlier. As I understand it, when the melanoma study was, I guess, completed enrollment, I think you guys continued opening new sites, expanding kind of the education, the treatment site education footprint there. Do you have a sense for the number of sites that you've interacted with and that have conducted TIL therapy? And how that compares on a percentage basis to kind of the target number of sites ultimately commercially? Like how far are you already in terms of interacting with physicians?

Yes. That's a good question. And I think we mentioned that in the past, the fact that, unfortunately, we had some delay in the BLA submission. It's an opportunity for us to actually upside being even better prepared. And the number we always disclose is that we will at least have 40 sites at launch ready for commercialization. We say it will be a mix of clinical sites on top of new sites. Of course, we are targeting the top cancer center sites in the U.S. I think this is -- and we believe it's the right number to start, and we will obviously expand throughout the years. But again, to answer your question, the target is at least 40 sites.

Okay. Excellent. Maybe a question for Madan. I guess regarding the lung cancer data, it would be great if you could kind of just review that for us. And then specifically, I would love to hear just the differences in patient population between the basket study, the Cohort 3B of that basket study relative to this potentially registrational Phase II. Like where -- to what extent are those patient populations similar and different?

Thank you, Ben, for that question. So at SITC last week, we presented results from a signal finding cohort of 28 patients who have heavily treated non-small cell lung cancer and had progressed after immune checkpoint inhibitor therapy. So as a context, majority of the patients with advanced lung cancer are treated with first-line ICI plus/minus chemotherapy. And we all know that most of these patients progress after their first-line chemotherapy and you really need effective strategies. So Cohort 3B was the first experience of Iovance in advanced non-small cell lung cancer. And again, to emphasize this with a signal-finding study in a multicenter study with a centralized manufacturing process. And the objective response rate was 21.4% in the full analysis of that. That means all the patients who got the TIL product. But 25% in the efficacy evaluable set, the efficacy valuable set was the subset of patients that reached their first assessment. I think it's important to note that 1 patient who achieved a complete remission and 1 PR are ongoing at 9.8 months. I think if you look at the 6 patients who have responded, the responses were seen across a spectrum of things, patients who had received multiple prior therapies, all of the responders had seen at least 2 lines of therapy. Everybody had seen a checkpoint inhibitor. And 1 patient has actually had 2 regimens of checkpoint inhibitor. There were 3 responders whose best objective response to the prior checkpoint inhibitor was progressive disease. We had responders who are PD-L1 negative and PD-L1 positive. There were responders who had KRAS mutation. So this was really a very heterogenous cohort. So I think it's important to interpret this data in that context. This was a first foray into lung cancer, signal-finding study and the efficacy signal is strong. Obviously, the question really comes around the duration of respondents. DOR cannot be meaningfully interpreted when you have such a heterogeneous cohort. And that's a good segue into your sort of second part of your question, which was how does 3B overlap with LUN-202. So when LUN-202, the cohort is going to be very homogenous because the TIL therapy intervention is going to be in the second-line setting where patients have failed only their first line of checkpoint inhibitor plus chemotherapy. So I think we need to be in that space. We need to wait for the readout of the LUN-202, and we hope that coming in, in the second line should translate into a higher ORR and a more sustained DOR. So that's the way we will sort of think about it from a biological basis.

What's the bar for success in the Phase II population, just in terms of response rates? And if you can comment maybe also just on your expectations for duration of response.

Absolutely. Very valid question. So if you look at the ongoing Phase III studies by other industry partners, almost everybody is using docetaxel as the benchmark. And the ORR of docetaxel depending upon which data set you look like is somewhere between 9% and 13% with the progression-free survival in the neighborhood of around 4 to 4.5 months or there, right? So the question really is, is that the benchmark for TIL therapy? And that's basically we have to sort of decide and that would really decide what to expect from LUN-202. But our hope is that we can, in a very meaningful way beat that benchmark. And again, in a late-line setting, with 3B, we are seeing a 21.4%. So if you come in, in second line in homogenous setting, it should translate into a higher number and thus, it should be a meaningful delta between the current benchmark that is docetaxel.

Very interesting I want to ask a question about the melanoma data that you just presented at SITC and you presented early data at ASCO. This is a checkpoint inhibitor-naive melanoma patients. Can you just maybe talk about where those patients are treated today? And is there a case to be made for TILs to be used in the community?

It's a very good question. So let's sort of take it first from a scientific standpoint. I think what we've been able to show at ASCO '21 and now SITC '21 that in the checkpoint-naive patients with melanoma, we are getting an ORR that is really impressive. It is in the 60%-plus range. More importantly is the percentage of patients achieving a complete remission, right? That number was 30%, and that's unprecedented. If you look at pembrolizumab as the single agent, the ORR rate is 33% with a CR rate of around 6%, if that were to be the benchmark. You bring up a good question regarding where are these patients and how would we have access TIL therapy. And as Jean-Marc mentioned, right, our hope is to launch with 40 centers and tertiary and quarternary community centers or nonacademic centers that are doing cell therapy that is very much part of the launch plan. So we expect that these centers will contribute in a meaningful way to clinical trial accrual and down the road into the ICI-naive population as well.

Excellent. Okay. You have -- sorry to go back to the lung cancer, there's actually one other question I wanted to address. You have a third generation process, TIL manufacturing process. I think you've talked about this being implemented in head and neck. This also looks like it's being implemented in lung cancer and PD-L1 expression status of less than 1%. Why focus on the less than 1% and not do that more broadly?

Yes, absolutely. It's a very good question. So I think the construct of the LUN-202 study is there are 3 cohorts. Cohort 1 and 2 are stratified by PD-L1 status, that 40 patients into each. And Cohort 3 is an exploratory cohort where we are asking the question, can we embark on a core biopsy as a starting material because there is going to be a subset of lung cancer patients which may not have an accessible lesion by surgical resection or they may not be a candidate for a surgical resection and can these patients benefit from a core biopsy. So we are teaming up the core biopsy with the Gen 3 process, which is a 16-day manufacturing process that's where the patient wait time for their own product is really sort of compressed over there. Regarding the PD-L1 status. So in non-small cell lung cancer, as you all know, PD-L1 is a validated biomarker, which has therapeutic implications. And what we wanted to do is to see basically if in the PD-L1 low cohort, because these patients really do not have a whole lot of options after they have failed their first-line chemotherapy. They're typically not eligible for checkpoint inhibitor-based clinical trials. So I think it's sort of a higher unmet need group. So we wanted to basically explore in this population if combining a core box, even the Gen 3 process can address any further unmet need.

Is the Gen 3 process going to be kind of the go-forward process in head and neck? Or you still kind of evaluating both Gen 2 and 3 there?

I think we are evaluating. I think we're continuing to sort of enroll patients and kind of see how the biology plays out and then go from there. Obviously, both strategically and from a patient-centric view trying to compress the time line for the patient is of utmost importance to us and to the patient.

Okay. Okay. Excellent. And maybe just a clarification in head and neck.

I think as long -- as soon as we have some meaningful data to share, we will definitely try and update in a medical congress meeting.

Okay. Excellent. Let's talk about some of the earlier pipeline. You licensed an IL-2 analog from Novartis, IOV-3001. Can you maybe just talk about the design of that asset? Just walk us through kind of the current status of the program. Just really specifically curious if this -- if the plan is to implement this really alongside of TILs? Or could this be kind of a therapeutic in its own right?

That's a good question. So I think our strategic goal is to really refine the entire sort of TIL regimen platform. And I think conceptually, you can think about it as lymphodepletion. What is the ideal replacement for aldesleukin and how do you make your TIL product kind of more potent. So IOV-3001 really addresses what is the alternative to aldesleukin, right? Because aldesleukin has a superb side effect profile. And the question is, can we kind of look -- make that product much more safer. And that's where IOV-3001 comes in. So we are on track in terms of -- it's going to be an IND-enabling study and we hope to enter the clinic as soon as possible. So currently, we are thinking about that as sort of alongside the TIL regimen.

Okay. And so I think -- I guess is the hypothesis then you could extend this beyond sort of the typical short course that's used with aldesleukin?

I think it depends upon kind of all the PK/PD work that is sort of ongoing right now or whether it's just to support the TIL or is it going to be ongoing administration I think, so stay tuned for that.

Okay. Okay. And then just to make sure I understand. So this is also being -- I guess it could potentially also be used in the manufacturing process, the expansion of the TILs prior to administration. Is that...

I would say, I don't think we are ready to provide any guidance on that whether that's going to be implemented in the manufacturing process versus just on the clinical side.

Okay. Just curious, just in terms of the actual TIL process, just a long, I guess, piggybacking on this conversation, when TILs are extracted out of biopsy, does that include all species of T cells, like would that also include T regs?

This is a very good question. So typically, when we fragment the tumor, right? So we use the fragmentation methodology, essentially all T cells egress out. Now the way to address -- and we have shown this in I believe at ESMO a couple of years ago that our manufacturing process when we manufacture the TILs, the effect of T cells go up. The T regs are actually down regulated. The PD-1 expression is down regulated. Also keep in mind that the non-myeloablative lymphodepletion that these patients receive prior to the administration of the TIL is also targeting the T regs that are still in the host, to try and suppress them as much as possible, to give the TILs a maximum opportunity to produce its efficacy.

Awesome. Okay. Okay. Let's talk about the CLO program. I guess how does IOV-2001 -- I guess, first, how does that differ from lifileucel? And then just when can we expect sort of initial data here?

Absolutely. So in the conventional TIL platform, the starting material is the tumor and CLL where the tumor is in the blood. So the hypothetical question is are the T cells in the blood "analogous" to the tumor infiltrating lymphocytes, which I think there is many of signs to suggest that. So the way IOV-2001 works is we basically get a patient blood sample. It's not an apheresis product, which is kind of what is used in CAR T cells. So it is just a peripheral blood draw. And then we amplify the TILs in a 9-day manufacturing process. And then similar to the Gen 2 platform, the patients get the nonmyeloablative lymphodepletion, then they get their peripheral blood lymphocyte product or PBL, followed by the IL-2. So the way it differs is the TILs are actually in the blood versus when we go into the tumor. The manufacturing process is shorter. It's 9 days versus the convention of 20 days.

What enables that shorter manufacturing process? Is it just -- do you just get more starting material by drawing from the blood?

I think the kinetics of the T cells that are floating around in the blood versus that are resident in the tumor are just different. So that we take advantage of those biological differences in the manufacturing side.

Okay. Okay. Very interesting. Okay. Let's talk about -- so IOV-4001. I think this is another conceptually very interesting program. Just could you talk about this. And is it fair to say that TIL plus pembro, what you've shown so far is indicative of sort of the activity that we could expect from this?

That's a very good question. So I think we definitely believe in the polyclonality of the TIL. So the question we are asking is if you get into the landscape of genetically editing the TIL, can you edit other targets? So PD-1 is a natural target, the natural logical target to edit, and that's what is IOV-4001. So the hope is that the PD-1-edited TIL is more potent than the nonedited and obviously needs to be tested in the late-line setting. But conceptually, 4001 could basically aggregate the need of systemic anti-PD-1 therapy as well. So it could potentially be tested in earlier treatment settings down the road. But again, it's a logical progression, right? So we have to again establish the safety, the efficacy and then continue to move it forward as we've been doing with the Gen 2 platform in melanoma. You start in the late-line setting, and then you test it in the frontline setting.

Okay. Okay. Super cool. Like what's on the table in terms of other edits that you could potentially implement? Are there any sort of limitations? Like could you look at other checkpoint inhibitor receptors? Or even other activating receptors, I think we've seen another -- a number of programs look at like the IL-15 sort of membrane-bound construct. I don't -- any thoughts on that?

Yes, absolutely. So we've not provided any further guidance on what other targets are we going after, but I think this is where really science needs to kind of guide those decisions. How do you make your TILs more potent? How do you enable the TILs to grow effectively in the body, while instead of not being "dependent" on systemic IL-2 administration? So one of the strategies that you mentioned, right, the cytokine-tethering technology of IL-15. But I think that's all within scope. We are looking at all aspects of it.

Excellent. Is there a limitation to the number of modifications you could make during the manufacturing process?

I'm sure there are manufacturing limitations, the scientific limitations, and we need to be really cautious as we get into more complex editing.

Yes. Okay. Okay. Well, excellent. So we have about 1.5 minutes. Maybe Jean-Marc, a question for you. Could you just kind of talk about current cash position and sort of the runway you expect to run away with it?

Yes. So thank you, Ben. So we disclosed at the end of September, we have $660 million in cash. So this is a strong cash position that will be well into 2023 for us. So we can definitely finance our operating plan, our clinical pipeline development, commercial manufacturing readiness. And we also disclosed that we don't have any need of immediate -- immediate need of raising capital. So strong cash position.

Okay. And then maybe in the last 30 seconds, 1 question that came through. So the potency assay work that you're doing in melanoma, I think you've mentioned is going to have some application to cervical cancer. But is that -- should that have application across the pipeline to lung and elsewhere? Or would you see some more indication specific work that needs to be done there?

No, no. Clearly, we are really, I would say, indication agnostic, meaning the potency assays we're developing will answer any kind of indication. We'll release assay in the commercial setting for any kind of solid tumor.

Yes. Excellent. Well, I think we're out of time. Thank you both for the conversation. Really appreciate it.

Thank you, Ben. I appreciate it. Bye.