Good day, and thank you for standing by. Welcome to the Iovance Biotherapeutics Investor Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Sara Pellegrino, Vice President of Investor Relations. Please go ahead.
Thank you, operator. Good morning, and thank you for joining us to discuss regulatory and clinical updates for lifileucel in metastatic melanoma. During today's call, Dr. Frederick Vogt, our Interim President and Chief Executive Officer, will highlight the positive FDA feedback on our potency assay matrix to support our planned BLA submission. Then Dr. Friedrich Finckenstein, our Chief Medical Officer, will further define our strategy for TIL combination therapy in frontline melanoma. Following these updates, we will hold a Q&A session. Additional Iovance team members taking part in the Q&A include Jean-Marc Bellemin, our Chief Financial Officer, Dr. Igor Bilinsky, our Chief Operating Officer, Dr. Madan Jagasia, SVP of Medical Affairs, Dr. Raj Puri, EVP of Regulatory Strategy and Translational Medicine, and Mr. Jim Ziegler, SVP Commercial.
Yesterday afternoon, we issued a press release that can be found on our website at iovance.com, which includes regulatory and clinical updates for lifileucel and melanoma. As a reminder, statements made during this call will include forward-looking statements regarding Iovance's goals, business focus, business plans, clinical trials and regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statement. With that, I will turn the call over to Fred.
Thank you, Sarah, and good morning, everyone. I'm excited to hold this morning's call to highlight recent regulatory and clinical updates for lifileucel and melanoma. I'll begin with the positive FDA feedback on our potency assay matrix to support our planned BLA submission. This FDA feedback gives us confidence in our BLA submission and was also favorable towards our proprietary cell co-culture assay included in our potency assay matrix. As many of you know, we've been working hard at engaging the FDA on an ongoing basis to gain this alignment on potency assays. This recent FDA feedback is a major milestone that brings us closer to a BLA submission and to offering a new treatment option for melanoma patients who have an urgent need after failing anti-PD-1 therapy. This is a tremendous accomplishment for the Iovance team on behalf of the patients we serve.
We're extremely proud of our team and their successful collaboration in getting to this point, as well as their commitment to rapidly move towards BLA submission. As noted in yesterday's press release and based on the FDA response, we now expect to request a pre-BLA meeting in July and the complete BLA submission August of this year. All activities supporting the BLA, including completion of remaining activities for the potency assay matrix, read out of the melanoma cohort for clinical data by independent review committee and manufacturing facility readiness of the Iovance Cell Therapy Center, or iCTC, and our contract manufacturers and supply chain are on track to be complete for the BLA submission. Submitting the first BLA for TIL therapy and further developing our pipeline are central to our mission to be the global leader in innovating, developing, and delivering TIL therapy for people with cancer.
As we look to establish TIL therapies as the next paradigm-shifting class of therapy for solid tumor cancer patients, we are strategic in how we expand TIL therapies into new indications and move into earlier treatment settings such as frontline melanoma. With this in mind, we announced clinical data updates and plans for a phase III study in frontline melanoma with yesterday's press release. Friedrich will walk through the details of the frontline melanoma update right now. Friedrich?
Thank you, Fred. I'm pleased to talk more about the opportunity for more melanoma patients to receive lifileucel in combination with pembrolizumab when they are earlier in their disease. In yesterday's press release, we provided updated results from Cohort 1A in our IOV-COM-202 study in solid tumors. Cohort 1A includes patients with metastatic melanoma who were naive to prior treatment with anti-PD-1 immune checkpoint inhibitors, and they received lifileucel in combination with pembrolizumab. The most recent data cut is for 12 patients as of January 2022. This data set includes two additional patients since our last update at SITC 2021, and both patients are confirmed partial responders. Among all 12 patients with available data, the key takeaways are as follows. The overall response rate, or ORR, is now 67%.
Eight of the 12 patients had a confirmed objective response per RECIST 1.1, including three complete responses and five partial responses. Again, all responders were confirmed responses. Six of the eight responders had ongoing responses, and five responders had a duration of response of more than one year. Although this is only 12 initial patients, we continue to be very impressed with the ORR, the CR rate, and duration of responses we have seen so far. For context on the unmet need, pembrolizumab monotherapy demonstrated a 33% ORR and a 6% CR in metastatic melanoma.
The FDA previously granted Fast Track designation for lifileucel in combination with pembrolizumab for the treatment of ICI-naive metastatic melanoma based on the unmet medical need and potential advantages for this combination over available care. This data suggests that there is a significant opportunity to improve longer term benefits for melanoma patients using our combination approach, and we look forward to beginning a phase III study in frontline melanoma, which we are targeting for late 2022. I'll be available to answer questions during the Q&A session, which we expect to begin now. Operator?
To ask a question at this time, please press star then one on your telephone. To withdraw your question, press the pound key. Our first question comes from Michael Jeffries. Your line is open.
Hi. Good morning. Can you hear me okay?
Yeah. Hi, Michael.
Hey. Hey, Fred. Two questions from us. First is you announced positive feedback from the FDA. Can you just shed a little bit of light as to what that actually entails and whether that's actually a full alignment with the FDA or 90% of the way there, or how much of it really is still sort of a sign-off during reviews. In other words, how confident are you that you've got full alignment on the assay? The second question is, presuming you have run that on the phase 2b portion of the melanoma study, have you run that and are you prepared to present that data at ASCO? Thank you.
Thanks, Michael. Let me take the second question first. I think you're talking about Cohort 4 data, and you know, we haven't made any comments as to what we're presenting at ASCO, but we do at some point have to discuss Cohort 4 and then bring that data out and, you know, we may do that through a corporate press release. As I've said before, we may do that through multiple mechanisms, like press release followed by a medical meeting. We're not committing to any particular conference timeline for that data. It is very important for the BLA, though, so it's something that's on our mind. It's something we wanna discuss with everybody as soon as we can. On the first question, we've got really good alignment with FDA.
I don't know how to put a percentage on it, but what we've got is alignment on both the potency assay matrix and on the assays that are within the matrix, including the new assay that we've talked about. You know, we're feeling very, very comfortable about the BLA at this point.
Thank you.
Our next question comes from Mara Goldstein with Mizuho. Your line is open.
Great. Thanks so much for taking the question. First question I have is really on the pre-BLA meeting, and I'm curious about the nature of that meeting, given the prior meeting that was held on a pre-BLA perspective. You know, aside from the potency issue, my understanding of the characterization of that meeting was that you had everything that you needed and instructions from FDA from a filing perspective for lifileucel at that point other than the potency. Maybe if you could just review that with us. Then secondarily, also at that time, going back to that first pre-BLA meeting discussion of the cervical program and what you would need to do there. You know, are there any further updates as it relates to that?
The third question I just had is really on the combination study of lifileucel and pembrolizumab, and trying to understand the nature of that study now that, you know, there is another checkpoint plus another novel therapy in the market for first line previously untreated metastatic melanoma.
Sure. The pre-BLA meeting is a really important step. It's a very useful interaction. Just as a reminder, up until now we've been talking about meetings and interactions that are primarily focused on the potency assay and potency assay matrix. At the pre-BLA meeting, we do expect to have interactions about other things, including clinical topics. Actually that'll really is the focus of the pre-BLA meeting, clinical safety and other parts of the dossier that are gonna be filed. That interaction is really not, you can think of it as sort of de-linked in some respects from the discussion that we're having now about potency assay alignment. You know, we still have to have that meeting. The vast majority of sponsors have a pre-BLA meeting.
It's highly recommended by the agency to have that before you submit a BLA. On cervical. Cervical has been, as you know, affected by the approval of pembro as a frontline, and we're still reevaluating that strategy and that when we talk, when we say we're reevaluating that working with the FDA, that's essentially like a separate track. We're having other meetings with FDA there and discussions with FDA about how to proceed with that program. I would consider that a separate work stream from the melanoma BLA, which is on a much, much faster track right now. With cervical, we do plan to come back and talk about that more once we have more details about exactly what our strategy is. As you probably know, we're focused on the post-checkpoint, post-PD-1 cervical landscape right now.
Finally on Nivo-Rela, you're referring to Nivo-Rela, I assume, with the recent approval.
Correct.
Yes, we studied that landscape. You know, in frontline right now, pembro commands a good share of the market. Nivo-Rela will take some share of that. Nivo alone takes some share. Ipi-Nivo takes a share. You know, they're all gonna take, you know, roughly a fifth of the market to a fourth of the market as things play out. At least that's how we think it will play out. If you look at our data in frontline melanoma, it's really compelling. When we think in a phase III study, once we design it and talk a little bit more about it's something where lifileucel plus pembrolizumab can offer some advantages over all the therapies that are out there, and we should be able to run a study that demonstrates that.
Okay. Thank you.
Our next question comes from Joseph Pantginis with H.C. Wainwright. Your line is open.
Hi, everybody. Good morning, and thanks for taking the question. Very nice milestone today, and thanks for the details. I guess I wanted to have a little bit of a forward-looking question here. First, with regard to these processes and assays in your potency matrix, first off, what would you say the overall impact it's had on your overall manufacturing plans and any, you know, significant changes that need to be made for your overall logistics? Second, and I think more important, when you look at the commercial profile, how you feel these new assays may or may not impact your projected COGS.
Sure. In terms of our capacity and our manufacturing as we do it today, we don't see much impact from the potency assay matrix alignment that we've got with FDA. We have QC labs, of course, associated with our facilities that are capable of doing all these tests, and we've spent a lot of time and effort getting them up to tip-top shape so they can do this. We really don't see that as a major milestone. Of course, they have to execute, and we have, you know, a lot of work to do, but that's stuff that can be done. In terms of COGS, yes, they have a minimal impact, but it's really, you know.
We don't go into details of this, but let me just say it's really rather insignificant overall in the grand scheme of COGS for cell therapy to add a test here, take a test away there.
That's very good to hear. Thanks a lot.
Thank you. Our next question comes from Mark Breidenbach with the Oppenheimer. Your line is open.
Hey, good morning, and thanks for taking the question. I guess I'm wondering if you're seeing the proprietary cell co-culture assay that you mentioned as, is this something you have IP around? Is this something that could potentially be a barrier for competing TIL therapy developers? The second question is, with respect to the planned phase III trial in front-line melanoma, should we be viewing the RELATIVITY-047 study as kind of a template in terms of study size and comparator arms and endpoints? Or do you envision something maybe smaller than that study? Thanks for taking the questions.
Sure. Thanks, Mark. Well, why don't I take the first one, and then I'll ask Friedrich to answer the second one. Yeah, we have intellectual property around the assay, and we've protected that thoroughly. We think that is highly useful in this space. We think the assay technologies are significant, and that's what we do with all of our intellectual property at Iovance. I can't really give you much more details yet. Some of that IP is still in the works or is not yet published, but it's there. Friedrich, do you wanna answer the second question?
Sure. Happy to. Yes, I think that's a good question, and the answer is fairly obvious. So the Relativity study obviously compared a new combination versus monotherapy, and that's usually what the regulators want to see in order to understand the contribution of components, right? In that regard, the pattern when we are bringing forward the TIL plus pembro combination will be similar. Whether the populations and/or the sample sizes will be the same is really subject to additional discussions, also to alignment with the FDA. I don't think that we're ready to share a lot of details on that at this point.
I would just say stay in the loop and we'll update on it as we find out.
Okay. Maybe one quick follow-up, just with regard to the latest data cut for Cohort 1-A. I don't know if you gave us a median follow-up time with this data cut. Maybe Frederick, you could also tell us specifically for the two new partial responders, how long their responses have been ongoing for.
Yeah. We haven't shared the median follow-up time yet. If you go and look at the data that we shared at SITC, which had a data cut just about three to four months prior to this one, I think you can figure it out. The follow-up obviously ranges from something that is shorter, which would be kind of some of these two new additional patients, to the longer follow-up of the patient that had more than two years' follow-up. You were asking about the two additional patients. Can you repeat that, please? I'm sorry.
Just in terms of how long their responses have been lasting for.
Well, again, these patients were treated in the interval of the data cuts, right? Their follow-up would be between three and six months each. Both of these are ongoing. Both of them also are confirmed, right? These are not unconfirmed, just now identified responders. These have been on long enough to have confirmed responses, and the responses are ongoing.
Okay, perfect. Thank you so much for taking the questions.
Thank you. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open.
Good morning, guys. It's Uncertain on for Tyler. Congrats on all the progress
following the latest FDA feedback, could you just give us your latest characterization of the matrix? What specific activation markers are included? How are they being measured exactly?
Yeah, we're not disclosing that publicly for the sensitivity of it, which is fairly typical in this space. What I can tell you is that as part of the assay, we have a cell co-culture assay, which we talked about in our press release, which is an important part of the assay matrix. We also have some additional assays in the matrix that are other measures of activation and other measures of T-cell performance that are based on our extensive data set, extensive experience with manufacturing TIL products and treating patients.
Great. Thank you. Just one follow-up question. Does activation typically correlate with response, and is it possible to quantify this?
No, we have not. We don't see correlations in that area, in the terms of correlations that would be statistically meaningful. There's part of the reasons we use a matrix is because the, you know, there is no clear correlation, just like with CAR T between one of our activation measures and the actual response received, you know, that the patient obtains. But what we do instead is we use a matrix which looks at many different properties of the TIL product, and we, based on our manufacturing history and experience of studying those properties, we're able to set specifications and determine if the product is likely to offer the patients commercially the same clinical benefit that the patients in the trial had.
Great. Thank you.
Thank you. Our next question comes from Colleen Kusy with Baird. Your line is open.
Great. Good morning and congrats on the regulatory progress. Thanks for taking our question. Can you just talk to the reason for the gap between this feedback now and the pre-BLA meeting in July? Is that purely just FDA scheduling? Separately, now that you have this positive feedback on the potency assay matrix, how will you start incorporating that into your other development programs?
Yeah, Colleen, it is. It's a good point. It does take time to get meetings with the FDA, and they are busy and, you know, we're working as quickly as possible with them, but these things do take time. That's part of the reason for the gap. You have to take some time, but also we just have a schedule of activities that we were driving towards for our filing that need to be completed, across all areas of the BLA filing. And then your second. Can you repeat your second question again, Colleen? I'm sorry.
Yeah. Now that you have this positive feedback on the potency assay matrix, how will you start incorporating that into your other development programs?
Sure. It's great to have this. This functions as effectively a template for how we could potentially move forward with lifileucel in cervical and in non-small cell lung and in some of the other indications as well as the gene-edited TIL products. It gives us effectively like an anchor that we now know is likely to be the cornerstone of the approach. Now, that said, we have to adjust things as we go because the products are different and there may be things that FDA is interested in, and then we have to study those products carefully to see if their manufacturing history and properties are similar or different. There's always gonna be subtle maneuvers here with the matrix. But what it really does is it sets sort of the baseline floor for our matrix going forward.
Great. Thank you. One more quick one if I can add. Can you just talk about your latest thoughts around what type of review you're expecting, either accelerated or regular?
We expect it. We have RMAT designation. We are expecting a priority review.
Great. Thanks for taking our questions.
Thank you. Our next question comes from Joseph Catanzaro with Piper Sandler. Your line is open.
Hey, guys. Thanks for the update here. I maybe wanted to just follow up on something you just said, Fred, with regards to calendared logistics being part of the reason. I'm wondering if the slight push in the BLA filing is due to something explicit within the FDA feedback on potency, and if so, could you provide a little more detail on what you expect to continue working on past the prior first half 2022 guidance? And then is any more engagement with the FDA expected prior to the pre-BLA to discuss potency further? Thanks.
Let me go in reverse order. No, I don't think we plan much more engagement with FDA on the potency piece. We think this largely has resolved the issue. Now, going back to your first question, we do, based on the feedback we got from the FDA, want to complete some submissions that were short term on our horizon anyway. We want to get them in well in advance of the pre-BLA meeting, so there's time for the FDA to look at them and so on. Then as when Colleen asked her question, as I was mentioning, it does take some time to schedule these things. They occur on a 60-day timeline from the time you make the request all the way through to the meeting.
All that, when you stack it together, the fact that we wanna get some stuff in ahead of that's what's driving essentially the reset of the timelines a little bit here. Again, the timeline shift is very, very small here.
Okay. Got it. Thanks. That's helpful.
Thank you. Our next question comes from Asthika Goonewardene with Truist Securities. Your line is open.
Hi, guys. Thanks for taking my question, and congrats on the milestone here. A lot of questions have been answered, but I just, maybe since we've got Dr. Puri on the line, just want to ask Dr. Puri directly, what is your confidence that you've kind of crossed the finish line with the potency assay? Thanks.
Raj, you wanna go?
Yeah. Good morning. Based on the FDA comment, and the preparation we already have with the proprietary assay that Fred talked about, I'm pretty confident that FDA and us, we have come to an alignment.
Agreement on this potency assay and the potency assay metrics.
Awesome. Thank you very much, guys.
You're welcome.
Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open.
Hey, everyone. Thanks for taking our question. I guess our first one is kind of thinking about the calendar between now and August 31st. When would we expect that you guys would top-line data from Cohort 4 ahead of the pre-BLA meeting to kind of follow the comment you made earlier, Fred, that discussions of the clinical data would be part of that pre-BLA meeting in July. Should we expect between now and July that Cohort 4 data to be released?
Yeah, Madhu, that's possible for sure. I wouldn't say it's guaranteed, but it is one of the possibilities.
Okay.
Obviously one.
On the phase III trial, again, in frontline melanoma, I mean, kinda it was already asked what the RELATIVITY-047 as a template. Is there a kind of a notion of how you keep people on a therapy? Will the control arm be just kind of any potential PD-1 containing regimen, or would it really be locked into, say, just pembrolizumab or just PD-1 inhibitor? Like, how are you thinking about what the comparator arm needs to be to be most representative?
I can start, maybe Friedrich you can pick up. We haven't disclosed the full detail of this yet, but there's no reason we can't use something like pembrolizumab as the control arm. It is approved. You know, that said, we'll consider all the possibilities. Friedrich, do you wanna comment any further on that?
I think given where we are right now, I think we can't really go into a lot of details. But again, one thing to keep in mind, obviously pembro is an approved standard of care. Fred has spoken to kind of sort of how the providers are using these different options currently. And there are ways of designing a trial that would keep patients in the control arm. I think there's been examples in the past on how you can do that in that type of study.
Just to add a little bit to it, we're gonna balance this, you know, we're gonna balance that with enrollment considerations as well, as we wanna talk to the FDA about this and obviously get their input as soon as possible on this.
Excellent. Thank you.
Thank you. Our next question comes from Peter Lawson with Barclays.
Thanks.
Your line is open.
Thank you. Congrats on the news from the FDA. On the co-culture assay, what does that involve? Does that kinda capture the diversity of the TILs? Would that be. Could you use that as well for again multiple indications and combination?
Peter, yeah, that's it does capture the diversity of TIL neoantigen selectivity and the ability of TILs to TCR receptors on TILs to sense and detect and then destroy cancer cells expressing diverse neoantigen profiles. It does have applications across indications. We're studying that in more detail, but the core technology that we have in that area has been built now and is pretty thoroughly vetted. We intend to use that as a platform for a lot of things as we go forward. Could it change subtly as we go from indication to indication? Sure. We'll work on that.
Gotcha. Thank you. It sounds like Cohort 4 is kind of important to get in front of the FDA for that pre-BLA meeting. Is there anything else that we should be thinking about as well?
No, I mean, that's really the remaining major topic for the company. We have, obviously, to execute on a number of different areas ranging from, you know, the entire BLA filing and all the modules that are part of that over to readiness for pre-licensing inspections and so on. We've got all that going. As I mentioned earlier in my prepared remarks, you know, we've got everything is on track and running and the company is, you know, employees are doing a fantastic job working us towards what we hope will be a very successful BLA process.
The pre-BLA meeting, will that be announced when that's worked out around the date of that meeting?
We can't commit for sure, but it's the kind of thing that often a company in our position would announce, typically once you've had the meeting.
Gotcha. Okay. Thank you.
Thank you. Our next question comes from Ben with Stifel. Your line is open.
Hello, good morning. Congrats on the regulatory process, and thank you for taking our questions. This is Carolina on for Ben Burnett. What does it give you confidence that you will be able to submit the BLA for lifileucel in August soon after the pre-BLA meeting? Is that going to be sufficient time to address points raised by the agency in the meeting? And relatedly, do you have to run more clinical samples after the feedback you've got from the FDA? Thank you.
Yeah. We think a one-month gap, approximate give or take, is appropriate for us to be able to address any questions that occur at the pre-BLA meeting. Like I said earlier, we're trying to get everything done before the pre-BLA meeting, so it runs relatively smoothly and focuses on procedural issues more than anything. With respect to, I think you're referring to historical testing and the retention of clinical samples. Yes, we've got what we need there, and we've got that well under control right now.
Excellent. Thank you so much.
Thank you.
Thank you. Our next question comes from uncertain with Wells Fargo. Your line is open.
Good morning. Well, congratulations to the team. This is a terrific milestone. I think, and not unsurprisingly, our research suggests that Iovance has been pretty quiet in the marketplace. So just as a gauge your confidence in it being able to achieve rapid approval, would you be fully ready to launch immediately after approval? Or should we think about more staging or being perhaps more cautious until an approval and then adding the final pieces to the commercial team following approval? I guess, how should we think about spend this year and next year? Thank you.
Why don't I take the first part of that, and then we have Jim Ziegler, head of commercial, and he can probably tell you a little bit, and then maybe I can address the spend a little bit too, or Jean-Marc can jump in on that. We do anticipate launching, you know, essentially immediately after approval. With respect to our budget, we don't see a massive change there. We've been building the commercial organization. As we approach launch, obviously that increases and you wanna add some people there, but we don't see that as a huge change in our burn or anything like that. Jim, do you wanna talk a little bit about the launch itself?
Sure. Thanks, Fred. Hi, Nick. Right now we've just hired all of our key leadership roles for the team. We anticipate launching with 40 sites by launch. What that means is once we get FDA approval, there's still some small things that we'll need to do with the sites to ensure that they're ready to go. As you know, there's a treatment decision, then there's the process of scheduling the patient, doing the manufacturing run. It's probably still gonna be about six weeks or so from the time we get approval before that first patient is infused. We anticipate launching with about 40 sites.
Thank you. This concludes the question and answer session. I would now like to turn the call back over to Frederick Vogt for closing remarks.
Thank you again for joining this meeting or joining us this morning. I'd like to thank the Iovance team for all of her work and dedication on the potency assay matrix, going above and beyond on behalf of the melanoma patients who are urgently awaiting cell therapy. We're also grateful to patients and physicians who have been on this journey with us, in addition to our supportive shareholders and covering analysts. Please feel free to reach out to our investor relations team if you wish to follow up. Thank you all, and Good morning.