Thank you. Good afternoon. Welcome to Barclays Global Healthcare Conference in Miami. Do email myself or my colleagues if you, if you have any questions. My name is Peter Lawson. I'm one of the U.S. biotech analysts, covering midcap, oncology-related names at Barclays. I'm really delighted to have on stage with me, from Iovance, we've got Friedrich Finckenstein, Chief Medical Officer, and Igor Bilinsky , Chief Operating Officer. Maybe the first question for us, of course, I know everybody today, probably, and until the end of the month, is just where you are for BLA filing and how that process is... If you're almost complete and what last steps are required.
Thanks, Peter, and good afternoon, everyone. We are on track to complete the BLA submission this quarter. We have completed all the supplemental assay validation work, and we're now finalizing the sections of the BLA for submission so that the target remains to complete the rolling BLA this quarter, and we're confident that we will achieve the target.
Okay. I guess with your presence here today, I guess you feel pretty confident that everything's moving along fast?
Indeed. There's been a lot of work. The team's done a tremendous job, and we're finalizing the sections of the BLA right now.
Got you. Then what should we expect to see once the BLA is filed? The acceptance within the FDA after 60 days, what other time points should we be thinking about?
Once the rolling BLAs completion is submitted, yes, the next step will be acceptance of the submission by the FDA. That should occur in 60 days. At the time of acceptance, we also expect to get the PDUFA date. We expect to receive the priority review and at the time of acceptance, we should get confirmation on that. Then, we'll maybe talk about this later in the discussion, but expect to potentially get approval and launch later this year.
Perfect. Then what gives you the confidence around, an accelerated review period?
As you know, lifileucel for advanced melanoma has an RMAT designation, Regenerative Medicine Advanced Therapy. Based on that, based also on the high medical need in that setting where patients have no other approved options, we believe the likelihood of a priority review is high.
Got you. Between BLA filing and, you know, I guess post acceptance, how should we be thinking about other steps? Is there, you know, manufacturing site reviews or what other processes will you be going through?
another important step and during the review process is inspections by the FDA of the manufacturing facility or PLI, pre-license inspection. We expect that the FDA will inspect our ICTC, Iovance Cell Therapy Center, as well as our contract manufacturer's facility. Typically, that occurs somewhere in the middle of the review cycle. We expect to get more information of that on the timing, probably a couple of months after the BLA is accepted.
Okay. I guess you can communicate that on quarterly calls or analyst meetings, et cetera, to kind of give updates, blow-by-blow updates until approval.
I expect we'll give some updates. Certainly, I expect we'll give an update once the BLA submission is completed. I expect we'll give an update when the submission is accepted. Those will be the important near-term milestones.
Got you. Okay. As we think about the label, what's the kind of current thinking about what's included in the label, whether it's pooled, whether it's just Cohort 4?
As part of the pre-BLA meeting we got positive feedback from the FDA on the data. Also on our important CRS station got additional input, as you know, after that. Part of the feedback was also that the FDA is envisioning using Cohort 2 potentially as supportive of the pivotal data in Cohort 4. Also indicating that a pooled data set could have the same function. We think that Cohort 2 data will be reflected in the label in basically three scenarios. At a minimum, and that's, I think, safe to assume the FDA will include data from Cohort 2 in the safety section because the FDA likes larger safety data sets.
The best-case scenario, at least from our view, would be if they would then also reflect the efficacy in the pooled data set. Apparently, I am feedbacking. It's good feedback. Can you not hear me at all?
Yeah.
Is that better? Okay. I can't look at you, I'm sorry.
It's okay.
The best-case scenario is for the efficacy data to be reflected based on the pooled data set between Cohort 2 and 4 as well, so basically matching the safety data. There's a mid-case scenario by which the data would be presented separately, but the Cohort 2 data would make it into the label. That's ultimately FDA's decision, and we'll negotiate, but ultimately FDA will make a call on that.
Got you. I know we've had feedback from some physicians that are just like, well, we know the data, so it really doesn't matter what's in the label. I mean, how much credence is there to that? How important is it to get as much data in the label as possible?
Well, I think there's obviously other audiences, other people who review the label. You're right. Scientifically, the data from the pooled data set is out there. It looks very convincing. We presented that at ASCO here, and that's what the prescribers and the decision-makers on the clinical side will use, right? Having the pooled data in the label might help us with negotiating and communicating with other stakeholders as part of the launch.
Gotcha. Is it important to have the pooled data in there for reimbursement or pricing?
That would be one of the things that's favorable, yes.
Gotcha. How do you think that can change based upon having pooled or not having pooled data? What's the-
Well.
-updown?
You mean what is the update?
Like, as in having, the pooled... If you don't have the pooled data in there, how does that potentially impact pricing or reimbursement?
I'm not sure I can tell you exactly what the impact would be, but it can. The pooled data set is more patients, is a larger sample size, is more confidence on the data than if you present data on a small sample set.
Gotcha. Thank you. I guess the confirmatory trial, the TILVANCE-301.
Mm-hmm.
kind of how's that proceeding with the conversations with the FDA and just your thoughts about endpoints?
Right. What we have shared is that we have engaged with the FDA very early in the process of the design of this trial, have met with the FDA, have received positive input not just on the design but also on the timing of that interaction, which is important, right? That the FDA knows exactly where we are with this and what our plans are. We received feedback on some design elements. We achieved agreements on the endpoints, which we are very pleased with because we were able to agree on being able to use both ORR or PFS as dual primary endpoints, which is unusual for a solid tumor indication, but potentially is a reflection of FDA's, and that's me speculating, confidence in the response rates being meaningful in the context of melanoma data.
We are currently in startup activities, meaning we are reaching out to sites, going through startup and review and site activation processes.
Okay. remind me the trial design is a single-arm pembro?
It's a randomized study, with the experimental arm being lifileucel plus pembrolizumab, with the comparator arm of pembrolizumab monotherapy, a sample size of 670 patients randomized 1:1 into these, into the two arms. With the control arm patients having the option to cross over into lifileucel monotherapy after independent review source or verified confirmed progressive disease.
Gotcha. just the idea of using single-agent pembro-...
Mm-hmm.
in those patients.
Mm-hmm.
Does that kind of change the enrollment dynamics in any fashion?
It is, it'll have different impacts on enrollment and decisions to enroll depending on the local standards of care of where we would be going. Obviously, U.S. patients have a number of choices in the frontline setting. This is not the same in other geographic regions. We are planning on running this study as a global study, including patients from the U.S., from large cancer centers in the E.U., but also from sites beyond that. That is one way for us to manage this. What I should say is that the benefit of the pembro monotherapy arm is FDA's agreement with the design. FDA does like designs that allow you to clearly interpret study results as well as assess contribution of components.
There, a TIL plus pembro versus pembro is really the cleanest design.
Gotcha. Thank you.
Mm-hmm.
I mean, is it gonna be obvious from the outset that the patients are... they kind of know which arm they're on?
They will be randomized. They can, they sign informed consent just like any randomized study. They sign informed consent. They will go through screening. They get randomized, and at that time, they will be told in which arm they are randomized. This is not a blindable.
Yeah.
-design, right? Obviously, these patients, that, need to go through surgery, and then the TIL regimen, while the control arm patients only receive pembrolizumab, so that's not something that we can blind.
I guess we've seen the number of studies where PD-1 by itself has underperformed. We have what's, you know, package inserts, et cetera. How do you kind of triangulate what's gonna happen in your trial?
Well, it's a randomized design, right? We're... Other than our relapsed refractory treatment setting with the study with the results that are currently being submitted, this is a study that doesn't work based on benchmarks, but based on comparison to the control arm. Obviously, we make some assumptions when we design the trial, and we are assuming performance of the pembro monotherapy arm based on published studies.
Good. Primary endpoints, You're not using OS? Will that be a secondary?
OS is a key secondary endpoint. Obviously, we are designing the next trial, in regards to size and also expected duration in order to enable us to analyze overall survival. It's a key secondary endpoint. The primary endpoints, however, are ORR and PFS. The beauty of that is that ORR allows us a much, much faster readout and an earlier interim analysis that could potentially drive an accelerated approval in that setting, compared to PFS, and even more so compared to overall survival, because obviously it requires less follow-up, and you don't necessarily need to enroll the entire study population in order to cut the data.
Got you. Do you expect the trial to be, you know, more of ex-U.S. trial versus U.S.? What's the balance you expect?
We're taking all efforts to get on board as many sites as we can in the U.S. and European and beyond. We don't have a specific target in mind for how we end up. We're basically reaching out, and we will take what we can get.
Got you.
Mm-hmm.
Do you expect that we could see, I guess, data from the front line, was it IOV-COM-202 Cohort 1A, this year or?
That cohort is still enrolling. We did share encouraging results in first scientific meeting and then a corporate update last year, showing a response rate of 67% in an initial 12 patients with a CR rate of 25%, which is encouraging given the comparative performance. If you just look at the KEYNOTE-006 data in the label, you look at 33%-34% response rate and about 6% CR. We shared that last year. We gave an update earlier this year on the data that we're currently seeing being consistent with the results that we presented back then in nearly 20 patients.
We will continue enrolling this, we will share the data at the scientific meeting, but currently are not projecting when.
Got you. Thank you. I guess kind of a similar question just around Cohort 3A
Mm-hmm.
in the IOVA
Mm-hmm.
COM 202 study. Just when could we see an update around that?
We have committed to present more detailed, potentially updates also, on additional patients because as well as Cohort 1A, this cohort is still enrolling, so we might add some patients to the 17 patients that we reported on our top-line data earlier this year. We committed to presenting this data in 2023, but we have not specifically pointed out at which meeting and when this year.
Got you. When you speak to physicians and so for that early line, IO-naive population, kind of what number of patients do you need to see for the physicians to kind of view this as meaningful?
For me, the meaningfulness of these kind of, sort of, signal-generating data sets is always driven by two components, which is number one, the effect size. What's the response rate and how meaningful is the response rate, and obviously the sample size, as you say. This particular cohort was designed as a signal-generating cohort with a fairly broad inclusion, exclusion criteria that allowed to enroll somewhat heterogeneous populations. The only requirement really was patients had to be checkpoint inhibitor-naive. Now, you will see if you do that you will get patients enrolled who are completely treatment-naive in the advanced setting, patients who have received chemotherapy only, but not checkpoint inhibitor, or patients with driver mutations who might have received TKI or TKI plus chemo, but no checkpoint inhibitor.
All of these have their own benchmarks, and that's the context in which you have to see the data. For example, the treatment-naive patients, within this sample set of 17, we saw four confirmed responders. That gives you in a small sample set, a response rate of 80%. That is very meaningful when you compare it to what these patients would be seeing with combination chemotherapies plus pembro, which would be probably more in the 50% range.
Got you.
It's all a question of what's the meaningfulness of the ORR.
Yeah.
Then, the sample size providing kind of sort of the backdrop of confidence in the data.
Got you. I'd love to pivot back to just the commercialization strategy and kind of where you are for just being ready for further approval and ramping up.
We're actively working on that. Yes, BLA is one goal here in the near term. PLI inspections is the next one, and then commercial readiness is the next goal. On which we're working on both the sales and marketing and the manufacturing side. Our commercial team actually has very strong cell therapy commercialization experience, and the team came from several companies with recent cell therapy commercial launches. The focus there is on access reimbursement and onboarding of authorized treatment centers. The plan is to have 40 authorized treatment centers onboarded around launch time, within three months of launch. The reason for 40 is based on the CAR-T experience, where the patient concentration is such that the top 40 CAR-T sites are responsible for about 80% of treated patients. On the manufacturing side, we expect.
We're getting ready for a robust demand at launch, that's what's driving our manufacturing preparation. As you know, we have capacity at our own facility is built of about more than 2,000 patients per year, now we're hiring the team and training the additional manufacturing team members to grow into that capacity and be ready at launch. These are the main activities at the moment.
Okay. I'd love to pick your brains with Rapamune next, but just like the idea of like what's the right patient for oncolytic virus versus TIL? How do you think that shakes out longer term, assuming both gain approval in melanoma?
Yeah. I should probably take that question. I think obviously with the intratumorally administered oncolytic virus, that is, that drives some differences in the populations, right? You need an injectable lesion for that. Patients going into a systemic administration after manufacturing of TIL need a resectable lesion that can provide starting material for TIL administration. I think maybe that would be one of the differences here. I think the data that are out there right now are hard to compare just because I don't think that we're looking at comparable populations based on these differences, but also based on number of prior lines of therapy and maybe some of the prognostic factors, such as tumor burden.
I think we'll have to generate some more data to see how this really pans out.
Gotcha. How would we try and classify that, like injectable lesions, the number of patients with injectable lesions versus resectable lesions?
It's a good question. I think, obviously an injectable lesion is not, it is likely to be a resectable lesion depending on number and sizes, but not every resectable lesion is necessarily an injectable lesion. Did I say this right? Yes.
Okay. Perfect. Thank you. Just those 40 sites you were talking about, kind of are they already trained? How do you kind of start that process, and how early do you start that process?
We're in the midst of it. You don't want to get the site onboarded too soon because the institutional experience may gradually decline over time. You need to do it just in time in a way for launch, and that's what we've been timing. The team's been onboarding the sites, again, with the expectation that we'll have 40 sites around the time of launch, and then they will be onboarded within a reasonably short time prior to launch.
Gotcha.
Some of those sites, maybe there are several segments there. Some or many of those sites are currently our clinical trial sites. Those sites already have a lot of experience with TIL therapy, and their onboarding process is customized based on their experience. Some of the other sites may be reputable NCI and centers with cell therapy experience but no TIL therapy experience. Again, the onboarding process is customized to meet their specific needs.
Gotcha. What's the overlap of those 40 with clinical trial sites?
It's a significant overlap.
You feel.
I feel like there's a Venn overlap. It's not 100%, but it's significant.
Gotcha. Most of them you're in that... They've already got experience. What do you do with those that's... Is there any training required?
There's always training required, and there's a lot of logistics that goes into onboarding a site and making sure that they're ready for commercial launch. Again, both from the logistics standpoint, reimbursement standpoint, access, all those criteria are important for getting a site onboarded. It could be as simple as where's the loading dock where the shipment needs to be delivered, which one do we use? I mean, those little details, everything needs to be worked out. Again, it's easier for a site that's been participating in our clinical trials, and a little different from a site that hasn't been participating in our trials.
Did that kind of 40 sites doing 80% of the volume, that's from CAR-T. Do you think you get a similar kind of setup for melanoma?
We expect to have a fairly similar concentration, and it should be similar to CAR-T based on in part on the geographic distribution of the centers and the area coverage that they have and referral patterns that in melanoma are a little different, but nonetheless, there are a lot of similarities.
Perfect. Thank you. If there's any questions from the audience. If not, we're good to go. Thank you so much. Thanks for your time.
Thank you for the question.
Thank you. It's a pleasure talking.
Thank you.