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

Thank you. Good afternoon. Welcome to Barclays Global Healthcare Conference in Miami. And do e-mail myself or my colleagues if do you have any questions. And my name is Peter Lawson. I'm one of the U.S. biotech analyst that covers mid-cap 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.

And maybe the first question for us, of course, 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 on -- what last steps are required?

Thanks, Peter, and good afternoon, everyone. So we are on track to complete the BLA submission this quarter. We have completed all the supplemental assay validation work, and we are now finalizing the sections of the BLA submission. So the target remains to complete the rolling BLA this quarter, and we're confident that we will achieve the targets.

Okay. I guess with your presence here today, I guess, I guess you feel pretty confident that everything is moving a little faster than...

Indeed, there's been a lot of work. The team has done a tremendous job, and we're finalizing the sections of the BLA right now.

Got you. And then what should we expect to see once the BLA is filed, so the acceptance of the FDA after 60 days? What are the time points should we be thinking about?

So once the rolling BLA's [ competition ] is submitted, yes, the next step will be acceptance of the submission by the FDA that should occur in 60 days. And at the time of acceptance, we also get -- expect to get the PDUFA date. We expect to receive the priority review and the time of acceptance, we should get confirmation of that. And then we'll maybe talk about it later in the discussion, but expect to potentially get approval and launch later this year.

Perfect. And then what gives you the confidence around [Audio Gap ] had an accelerated review period?

So as you know, lifileucel for advanced melanoma has an RMAT designation, regenerative medicine advanced therapy. Based on that, based also on the high unmet medical need in that setting where patients have no other approved options, we believe the likelihood of a priority is high.

Got you. And so -- and between BLA filing and except -- I guess, post acceptance, but how should we be thinking about other steps as there -- manufacturing site reviews? Or what are the processes that will be going through?

Another important step and during the review process is inspections by the FDA of the manufacturing facility or PLI for license inspection. We expect that the FDA will inspect our iCTC Iovance Cell Therapy Center as well as our [ contract ] manufacturers facility. Typically, that occurs somewhere in the middle of the review cycle. We expect to get more information on that -- on the timing probably a couple of months after the BLA is accepted.

Okay. And 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. And those will be the important near-term milestones.

Okay. And then as we think about the label, what's the kind of current thinking about what's included in the label, whether it's pulled, whether it's just to hope for...

Out of the 3 [ limiting ], we got positive feedback from the FDA on the data. Also on our potency, we got some additional input, as you know, after that. But part of the feedback was also that the FDA is in using Cohort 2, potentially supportive of the pivotal data in Cohort score. Also, [Technical Difficulty] same function. So we think that Cohort 2 data will be reflected in the label in basically 3 scenarios at the minimum. And that's, I think, safe to assume the FDA will include data from Cohort 2 safety ] because the FDA likes data sets. Then the best-case scenario, I think from our view would be that also [Technical Difficulty]. Apparently, I am getting feedback. Can you not hear me at all? Is that better? Okay. So I can't look at you, I'm sorry. So the best case scenario is that for the efficacy data to be reflected based on the pool of data sets between Cohort 2 and 4 as well. So basically matching the safety data. And then there is a mid-case scenario by which the data would be presented separately, but the Cohort 2 data would make it into the label. And that's ultimately FDA's decision. We will negotiate, but ultimately FDA will make a call on that.

Could 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 it's in the label." I mean how much credence is there to that? How important it is to get as much data in the label as possible?

Well, I think there's obviously other audiences, other people who review the label. But you're right. Scientifically, the data from the pool of data set is out there. It looks very convincing. We presented that as this last year. 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.

Got you. Is it important to have to pooled data in there for reimbursement or pricing?

That would be one of the things that , yes.

How do you think that can change, based upon having pooled or not having full data would start...

So you mean what is the update...

As in having -- 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 again, the pooled data set is more patients, is a larger size, is more confidence on the data than if you present data on a more small sample set.

Got you. And then I guess the confirmatory trial, the TILVANCE-301, kind of how is that proceeding with the conversations with the FDA and just thoughts about inputs.

Right. So what we have shared is that we have engaged with the FDA very early in the process of a 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 for ORR and PSS dual primary endpoints, which is unusual for a solid tumor indication, but potentially is a reflection of FDAs [ speculating ] confidence in the response rates being meaningful in the context of melanoma data. And we are currently in start-up activities, meaning we are reaching up to sites going to start-up and review and set activation processes.

Okay. And remind me, the trial design is a single-arm pembro?

So it's a randomized study was the experimental arm being lifileucel plus pembrolizumab, with the comparator arm of pembrolizumab monotherapy, sample size of 670 patients, randomized 1:1 into the 2 arms, with the control arm patients having the option to cross over into lysolusive monotherapy after independent review sort of verify confirmed progressive disease.

And just the idea of using single-agent pembro in those patients, does that kind of change the enrollment dynamics in any fashion?

It will have different impacts on enrollment and decisions to enroll, depending on the local standard 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 the study as a global study, including patients from the U.S., from large cancer centers in the EU, but also from sites beyond that. So 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. And there, a TIL plus pembro versus pembro is still the cleanest design.

I mean is it going to be obvious from the outset that the patients are -- they kind of know which arm they're on?

So they will be randomized, they are [ financed ] like any randomized study when they sign the [ form of consent ]. They will also go in screening. They get randomized. And at that time, they will be told in which arm they are randomized. This is not a [ blendable ] design. And 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 [ blend ].

And I guess you're saying the number of studies where PD-1 by itself has underperformed your package inserts, et cetera, but how do you kind of triangulate what's going to happen in your trial?

Well, it's a randomized design, right? So we're -- other than our [ deluxe ] refractory treatment setting with a study that -- 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 designed the trial, and we are assuming performance of the pembro monotherapy based on published service.

And primary endpoints, you're not using OS. What will be in a secondary...

So 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 is a key secondary endpoint. The primary endpoints are ORR and PSS. And the beauty is that ORR is a much, much faster, a lot of -- a much, much faster readout than, say, an earlier interim analysis that could potentially drive an accelerated approval in that setting compared to PSS and is more so compared to overall survival because obviously, it requires this follow-up and you don't necessarily need to enroll the entire study population in order to [ pool ] the data.

Do you expect the trial to be more of in an ex U.S. trial versus U.S., was the balance you'd expect?

So we're taking all efforts to get onboard as many sites as we can in the U.S. and Europe and beyond. We don't have a specific target in mind for how we end up with basically reaching out and where we'll take what we can get.

And do you expect that we could see data from the frontline, was it IOV-COM-202 Cohort 1 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. So if you just look at the KEYNOTE-006 data in the label, you look at 33% to 34% response rate and about 6% CR. So 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 to this. We will share the data at the scientific meeting, but currently are not projecting when.

And then I guess kind of a similar question just around Cohort 3A, higher [ VA ] COM-202 study. Just when could we see an update around that?

So we have committed to present more detail potentially updates also on additional patients because, as well as Cohort 1A, the 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. So we committed to presenting this data in 2023, but we have not specifically pointed out at which meeting and when with you.

Got you. When you speak to physicians, and so for that early-line [ iron-ave ] population, kind of what number of patients you need to see for the physicians to kind of view this as meaningful?

So for me, the meaningfulness of this kind of signal-generating data set is always driven by two components, which is number one, that's the effect size. So what's the response rate? And how meaningful is the response for it? 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 population. So the only requirement really was patients had to be checkpoint [ treatment ] naive. Now, you will see, if you do that, we will get patients enrolled who are completely treatment naive in the advanced setting, patients who have received chemotherapy on Lenvatinib checkpoint inhibitor or patients with driver mutations, who might have received TKI or TKI plus chemo, but no checkpoint inhibitor. All of these has their own benchmarks. And that's the context in which you have to see the data. For example, the treatment-naive patients, 5 within the sample set of 17, we saw 4 confirmed responders that gives you, in a small sample set, a response rate of 80%. And that is very meaningful when you compare it to what patients will be seeing with the combination of chemotherapies that would be probably more in the 50% range. [ Third ] is all the question of what's the meaningfulness of the ORR and then the sample size providing kind of sort of the backdrop of confidence in the data.

I love to pivot back to just the commercialization strategy and kind of where you are for just being ready for an approval and ramping up.

So that's -- we're actively working on that. So yes, BLA is one goal, our near-term PLI inspections is the next one. And the commercial readiness is the next goal on which we are working on both the sales and marketing and the manufacturing side. So our commercial team actually has very strong cell therapy commercialization experience. And the team came from several companies with recent cell therapy commercial launches. So 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 3 months of launch. And 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 robust demand at launch. So that's just 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, and now we're hiring the team and training the additional manufacturing team members to grow into that capacity and be ready at launch. So these are the main activities at the moment.

I'd love to pick your brains [ Friedrich ] next, but just 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 the gain approval and...

I probably take that question. So I think, obviously, with the intratumorally administered oncolytic virus, that drives some differences in the population, right, because you need an injectable lesion for that. Patients going into systemic administration after manufacturing of TIL, need a resectable lesion that can provide starting material for TIL administration. So 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 have -- that we're looking at comparable populations based on these differences, but also based on a number of prior lines of therapy and maybe some of the prognostic factors such as tumor burden. So I think we'll have to generate some more data to see what -- how this really pans out.

How would we try and classify that, like injectable lesions, number of patients with injectable lesions versus resectable lesions?

It's a good question. So I think, obviously, an injectable lesion is not -- it can -- it's likely to be a resectable lesion, depending on number and size. But not every resectable region is necessarily an injectable lesion. Did I say this right?

Yes. And just the 40 sites you are 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. So you don't want to get the site onboarded too soon because the institutional experience may gradually decline over time. So you need to do it just in time in a way for launch. And that's what we've been timing. The team has been onboarding these sites, again, with the expectation that we'll have 40 sites around the time of launch and that they will be onboarded within a reasonably short time prior to launch. And then some of those sites, so maybe there are several segments there. Some of many of those sites are currently our clinical trial sites. So those sites already have a lot of experience with TIL therapy. And their onboarding process is customized, based on their experience. And then some of the other sites may be reputable NCCN centers with cell therapy experience but no TIL therapy experience. And then again, the onboarding process is customized to meet their specific needs.

What's the overlap of those 40 with clinical trial sites?

It's a significant overlap. There's a Venn overlap. It's not 100%, but it's significant.

So most of them, you're in that -- they've already got experience. What do you do with those -- is there any training required?

There's always training required, and there's a lot of logistics that goes into onboarding a site to 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. And it could be as simple as [ worst ] of loading dock, where the shipment needs to be delivered, which one do we use? I mean those little details, everything is to be worked out. And 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.

And 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, the geographic distribution of the centers and the area coverage that they have in referral patterns that -- the melanoma, a little different, but nonetheless, there are a lot of similarities.

Perfect. Is there any questions from the audience? If not, we're good to go. So thank you so much. Thanks for your time.

Thank you.

Thank you.