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

Good day, and thank you for standing by. Welcome to the Iovance corporate update call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead.

Thank you, operator. Good morning, and thank you for joining our conference call to discuss the ongoing Biologics License Application, or BLA submission, for lifileucel, our new TIL therapy for patients with advanced melanoma. Earlier this morning, we issued a press release about the BLA submission that can also be found on our corporate website at iovance.com. On today's call, Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide a brief introduction and summary. Then we will hold a question-and-answer session where several members of our executive leadership team are available to participate. Dr. Igor Bilinsky, our Chief Operating Officer; Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine; Jim Ziegler, our Executive Vice President, Commercial; Jean-Marc Bellemin, our Chief Financial Officer; Dr. Friedrich Finckenstein, our Chief Medical Officer; and Dr. Madan Jagasia, our Executive Vice President, Medical Affairs. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, licenses and collaboration, cash position and expense 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 statements. With that, I will turn the call over to Fred.

Thank you, Sara, and good morning, everyone. We continue to make significant progress towards completing our BLA submission to the U.S. FDA and are close to the finish line. As we announced in our press release today, the FDA has requested that we provide supplemental information on assay validation and comparability data for lifileucel. The FDA's feedback is related to an amendment that we submitted in the third quarter to the ongoing investigational new drug or IND application for lifileucel at the FDA's request. We expect to address this feedback with requested supplemental information promptly. Our rolling BLA submission is planned for completion in the first quarter of next year after we address this FDA feedback. Addressing the FDA's feedback allows us to work towards a smooth BLA review process. I would like to emphasize that this FDA feedback to the IND application is valuable and specific, and the information they're asking for is limited to supplemental assay validation and site comparability information. Regarding the rolling BLA submission, the FDA remains supportive during the process and has not requested any additional information that we had not already planned to include in the submission, including our potency assay matrix, which has already received positive feedback. We also held a successful pre-BLA meeting in July where the FDA provided favorable feedback on the clinical efficacy data from Cohorts 2 and 4 of our C-144-01 clinical trial, including duration of follow-up, and agreed the clinical and safety data set was sufficient for BLA review. Lifileucel, if approved, may address the significant unmet medical need for melanoma patients who progress on or after anti-PD-1 therapy, for which there are no FDA-approved treatment options. The BLA submission for lifileucel is supported by positive clinical data from the C-144-01 clinical trial in patients with advanced melanoma. The detailed data set presented at SITC last week was extremely well received by the medical community. In addition, the Phase III trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma on track to begin in late 2022 is intended to serve as a confirmatory study and expect to be well underway at the time of potential approval. With that, I'll hand the call back to the operator to kick off the Q&A session.

[Operator Instructions] Our first question comes from the line of Peter Lawson with Barclays.

Fred, thanks for the updated guidance around the completion of the submission. Just curious around kind of what gives you the confidence around the 1Q completion term loan?

Yes, Peter, it's -- what they're asking for is relatively straightforward, short-term work that we can do rather quickly and get it done as early as possible in the first quarter. Actually, it's -- won't take that long at this sort of work. It is -- since lifileucel is a first-in-class therapy, there's some details on what FDA gave us that I think has never been seen before and is new to the space, so we're learning some things as they learn some things. And we think it's a supplemental validation really that's driving the whole thing and can do that fairly quickly.

Got you. And you mentioned about site comparability?

Yes. So that has to do with the validation. They're tied together basically. The FDA would like us to complete additional validation tasks so that they can then interpret the comparability between sites. And that's one of the reasons we want to get it done before the BLA filing, so that we have a very smooth process once we do complete the whole BLA submission.

And just a final question. I know that other people have got questions. But the potency assay, you already kind of got a sign off from that. Any additional assay validation is kind of unless -- we should consider as most minor additional data?

I think that's the good way to sign up here, yes. It's really -- it is, I think, relatively minor. The big picture is we think we're aligned with FDA. And actually, Raj Puri is on the call. Maybe, Raj, do you want to add a little bit to my answer there for Peter?

Yes. FDA has already accepted the potency assay, the principles and the mechanism of action. So basically, what we're trying to do is some validation of the assay in a specific way that the FDA would like to do. So we are, as Fred said, Peter, we're going to continue to work on this and should be done in the next 2 weeks, so we can go back and so with the amendment.

Our next question comes from the line of Michael Yee with Jefferies.

This is Yi Chi Song on for Mike. Two questions. The first, what new comments did you receive on the assay given positive feedback originally? If you could provide some additional clarity on that, that would be really helpful. And second question, by comparability information, do you mean validation that the product is comparable between CMO sites and iCTC? Or could you clarify that, please?

Yes. So the new information they're looking for is best described as supplemental validation information. So they -- like Raj said, they want some specific things as part of the validation of some of the assay information that we submitted, and that's pretty much all I can say. It's very, very, very technical in nature. And as the first product of this class coming through, the way that we're validating it is kind of commercially sensitive as well, so we really can't say a whole lot more. Not that anybody would be able to understand it, given the level of complexity associated with it. But it is routine and straightforward to do and we can get this done in a very short period of time. On the comparability, we're just talking about comparability between manufacturing sites, and that is depended on the assays so that can be interpreted. So you can think about it as the sites that we have involved in our network during the studies as well as in the future.

Our next question comes from the line of Madhu Kumar with Goldman Sachs.

I guess kind of one follow-up here on the confirmatory study. So you mentioned that you plan to have it well underway by the time of a potential approval. I guess kind of -- has the FDA given you explicit guidance as to what well underway meanings? And if not, like, how does the team interpret what is well underway to confirmatory study is?

Yes, Madhu. That's -- they haven't given -- they don't give a definition of well underway. What they have done it's been very comforting to us, they seem to be very comfortable with the time lines for the study. And they -- in fact, we -- we've gotten good feedback from them that we're on time and on track in that area. So we know that we're not late for this, and we know that we're not going to be one of these doghouses, is that they seems to be talking about right now for some of the other sponsors. So they don't really tell you though exactly what that means. I don't know if you saw, but [ Kyla ] from [indiscernible] were out, I think it was yesterday, the day before, out speaking and they've talked about just enrolling at the time of -- the study is enrolling at the time of accelerated approval. So that's one bit of guidance I've heard from them. But with us, it's been pretty -- it's been very positive that we will have this -- whatever they consider well underway to mean, we'll have that achieved at the time of approval.

Our next question comes from the line of Colleen Kusy with Baird.

Great. Can you clarify if the group revision that you had previously received favorable feedback on the assay from -- is the same team that you're now -- that is now requesting additional data? Or has this moved to some sort of different group at the FDA? And do you feel that after, the FDA cell therapy group will be satisfied with this last validation? Or do you think there's still consensus building that needs to happen to get this over the goal line?

It is, as far as I understand, the same group. There's not many members in that group, and Raj actually could probably help with this answer a little bit. And then maybe, Raj, would you want to take the second part of that as well?

Yes. Colleen. Yes, it's the same group of reviewers. The division has X number of people, so they don't have different various groups to review. And I think the reviewers who have the history of this file, they continue to review until the end, till they'll have a BLA. So that's the answer to your question number one. Number two, you're asking about -- I missed that part, Colleen. Can you restate?

Yes. Just -- I guess, how confident are you that this vast validation will be sufficient to build consensus among the group? Or do you think there's kind of further consensus building that needs to happen to get everybody comfortable with getting this over the goal line?

No, I think they're very, Colleen, they're very specific at asking what something -- for the validation. As you know that we can do validation in various different ways, and we did that one way and FDA wants it in a different way. And we can do that in the next only few weeks, we'll be done with that, and just submit back to the agency and also our complete out submission.

Our next question comes from the line of Tyler Van Buren with Cowen.

Regarding the short-term work and validation, I guess, just to be clear, does this include more potency assay runs? And are you redoing this with samples that have already been analyzed or these samples that have not yet been analyzed? And if so, is it related to Cohort 4 samples or Cohort 2 samples or both?

No, it's just a validation, Tyler. It doesn't involve the samples.

Okay, that's clear. And what do you think caused the FDA, I guess, to change their stance on this validation or they ask you to do it a different way?

I think fundamentally, it's a new product. Everything is new about it. We're breaking new ground, and there's just alignment that needs to be gained. The only precedent we have is really the CAR-T products, and things are done a little bit differently there. We've got a novel Cohort 2 matrix. And they -- as we progress through this filing, they just want to see things in a certain way, and we're going to work with them on it.

Our next question comes from the line of Mark Breidenbach with Oppenheimer.

Maybe just a quick one for Jean-Marc, actually. I was hoping you could comment on the potential impact of the delayed filing on your operational runway. I'm curious if this affects your previous cash guidance.

Yes. Thank you, Mark. So yes, obviously, we will be a mindful about the expenses, I mean the additional delays. Is the additional delays also in expenses? So you know our guidance is having sufficient cash into 2024. So actually, the fact we have some delay, we will go on tidying up our expenses, but it doesn't really impact any kind of operational readiness for commercialization, our current plan. We'll have just to be mindful again of this additional delay that will push some of the expenses at the later stage actually, so same guidance in terms of cash burn in the 2024.

Our next question comes from the line of Reni Benjamin with JMP Securities.

I think you mentioned earlier on in your prepared remarks that the feedback was based on an amendment that you submitted. Can you just give us a little bit of clarity as to what the amendment was?

Yes. FDA had asked us to submit some information to the IND, which is something you can do even while you're have a rolling BLA process to get their feedback when you have a RMAT designation. So we did that, and they provided a very helpful feedback as part of that, and that came in very quickly as opposed to going through the BLA review cycle and having it come much later. But it's related to -- the IND amendment was related to some of this validation and the feedback for the validations.

Okay. And then when we talk about the supplemental validation assays, are we saying assay or assays? Is this like -- is this multiple things that you have to address? And not to be kind of like coy about it, but what stops the FDA from coming and asking for a supplemental validation to the supplemental validation? Like, when does it kind of end?

Well, there's multiple assays involved in our potency matrix. So while we don't want to talk about the details, there's multiple factors at play here. However, all of them are, like Raj said, fairly straightforward. We're talking weeks here in terms of time lines to get the actual work done and turned around and submitted. What's stopping them from doing a supplemental supplement, I guess nothing. But we think, as Raj mentioned, the feedback that we got this time is very, very specific, and we think we can do exactly what they say. So while the regulator has authority to do whatever it wants effectively in this area, we think we're going to have the answers that they need in this round, and this should be the end of it for sure for these guys.

Got it. And then just one final one. Just regarding the CEO search, kind of where are we in the process? And is this -- is the filing maybe a gating item as well for anyone who's evaluating the company?

I can't say for sure whether that's a gating item. Obviously, the more progress the company makes, different CEO candidates, may look at it differently. But right now, the Board still continues their search and it's active, and we're looking at candidates. We don't have -- unfortunately, I don't have any updates for you today beyond that.

Good luck going forward.

Our next question comes from the line of Mara Goldstein with Mizuho.

Great. Just -- Can you or maybe just confirm for us that once this is completed, that this is the last component of the BLA that needs to be all submitted to be considered complete?

Mara, we're not describing the details of our rolling BLA submission. We've said that many times now, companies typically don't tell you exactly where they are in their submission. We told you we started in August, and we'll complete now in the first quarter of '23. I don't want to say this is the last component, but it is obviously -- just as you can see in the time line shift, it's obviously a component that is towards the tail end of everything that we're doing here. If you're asking because you're worried there might be additional stuff that's going to delay us further, no, we don't think so. We should be able to resolve it with this and then complete the submission.

Our next question comes from the line of Asthika Goonewardene with Truist.

This is Karina for Asthika. I might just have a question on the amendment to the IND. Does this have anything with the Cohort 4 data? And second question is update on your search for new CEO?

No, it doesn't have anything to do with the Cohort 4 data. It has to do with validation of the assays. And we got a question, I think it was Tyler and Mark that ask me the question. It doesn't require retesting or retain sample work or anything like that. And then as I mentioned before in the CEO search, the Board is actively looking for a CEO, and that work continues.

Our next question comes from the line of Joe Catanzaro with Piper Sandler.

Great. Maybe, Fred, you actually just answered this, but maybe not. I'm wondering with regards to comparability, whether there are any implications to how the clinical data are interpreted from study C-144? Or is it more so related to sort of commercial product and being able to tie back your clinical data ultimately with the commercial product that you'll generate?

I think it's more of the latter, Joe. Manufacturing site comparability is something you need to demonstrate that you've generated equivalent product at 2 different sites, whether they be 2 different clinical sites or 2 different manufacturing sites for the commercial marketplace, ultimately, the latter is what really matters for us and it's the most important. But really what it is, the way I think of site comparability is if the validations works out as we expect, the site comparability will follow. And that's really -- the two are tied together in that manner.

Our next question comes from the line of Ben Burnett with Stifel.

Question about the potential, I guess, real commercial implications of this. Has this changed the number of assays that would need to be done to release the product? And does this, in your view, change the release time?

No. No, it doesn't, Ben. It's the assays are already -- the matrix and the assays are already sort of on the time line, has already been developed. So this is really -- this is part of good manufacturing practices, GMP validation of how the assays are demonstrated to perform accurately and linearly, and reproducibly across different conditions.

Understood. Okay.

Not a change to the assay. Don't think about the change in the assay or assays.

Our next question comes from the line of Kelsey Goodwin with Guggenheim Partners (sic) [ Guggenheim Securities ].

I guess maybe just to confirm one from the prepared remarks. Did you say that this was data that you had already prepared or were preparing and planning just a bit anyway? Or it was additional data that they asked for? And then secondly, I guess, in terms of the variability and how the FDA sees it, I guess, how do you kind of anticipate the specs once approved? Are they going to be narrower than what you used in the clinic, and maybe implications there?

Kelsey, there is some additional data that we need to generate as part of this because it's a validation that involved laboratory steps. So as Raj, kind of mentioned earlier, it's not a very long endeavor. It only takes a little bit, but there is some additional work that needs to be done. And then we don't really anticipate any impact on the release specifications coming from this.

This concludes the question-and-answer session. I'd now like to hand the conference back over to Fred Vogt for closing remarks.

Okay. Thank you again for joining our update call. We are confident that we're close to completion of our rolling BLA submission in the first quarter of next year, and we look forward to advancing closer to potential approval. Please follow up with our Investor Relations team if you have questions or would like to talk. Thanks.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.