Replimune Group, Inc. (REPL) Earnings Call Transcript & Summary

Good morning. My name is Peter Lawson. I'm one of the biotech analysts at Barclays. And welcome to Miami and Barclays Global Healthcare Conference. I'm really pleased to have up on stage with me management from Replimune, so we've got Philip Astley-Sparke, CEO and founder. And love to talk about RP1 filing relapsed refractory melanoma and kind of we -- kind of series of other areas we'd like to cover as well with time.

But the first question really around the pass-through approval with RP1. Do you expect accelerated approval and off of the single-arm IGNYTE study?

So with RP1, our lead asset, we are still planning to establish a broad skin cancer franchise and the foundational study in that regard is indeed our study in PD-1 failed melanoma, which is a single-arm study. There are limited treatment options. So it's not actually totally clear what a control arm should be. Hence, we run a 140-patient single-arm registrational cohort. And yes, the route upon which it would be approved would be the accelerated approval pathway. We had a Type C meeting with the FDA last fall where they acknowledged the population is one of unmet need, and we also agreed the concept for a confirmatory study, which we would have to have underway by the time we make the filing, which is slated for the second half.

Okay. And then would we see another snapshot of data for IGNYTE before filing?

Yes, you will. The data we've disclosed to date, which shows approximately benefit in 1 in 3 patients by way of durable response. There was an interim look at that registrational cohort. 6 months after the last patient in, back in -- the back end of last year. The actual official primary trigger analysis is 12 months after the last patient in. That date was March 8. So it's just been passed. So we're now gathering the final data from the sites and the data will then go through independent central review. The data that we've disclosed to date has been investigated and declared response. And once we're through the central review process, we will disclose that data in the second half ahead of potentially filing the BLA.

Got you. Is there -- what's the risk as you go from independent review -- or investigator review to a central review as we think about ORR, CR rates, et cetera?

Yes, there's always obviously a risk to degradation of the response rate, although in this particular case, I do not think that is a material risk or will change the perception or shape of the data.

What gives you the confidence in?

Well, we've put a lot of our original scans actually on our website is when you're thinking about 30% reduction in the risk of tumor burden. It doesn't look like we have too many that are on the boundaries. So we'll have to see what the final result is. I think, typically, when these reviews are conducted sometimes 10% degradation of response. As I said, not really expecting it to be anything material that would change the perception of the data.

With the data you showed in the second half, would that be central review, investigative or both?

That would be central review. We won't present the data until it's been centrally reviewed from the official analysis.

Got you. Okay. And there's no point in turn that investigator reviewed data essentially or their interpretation of the data because central is the key here.

We're quite happy to update on the final investigator declared response as well. Yes.

Okay. Perfect. And then, are there any risks around delays, getting hold of the data, getting in to see data sets, et cetera, that we should be thinking about? I guess what worries you heading into that data set?

No, I don't think this is analogous to last year, where we did have delays in cutaneous squamous cell carcinoma. I think that was peculiar to the fact that complete response was an important endpoint and litigating complete response is a lot more involved than litigating simple response. So actually expecting this to be a relatively straightforward process. Started in the spring and should be through it by midyear.

The -- what's the bar for accelerated approval in terms of CRA duration and response we should be thinking about?

Yes. I mean, the FDA has set no bright line in terms of what the bar is. We actually set up our protocol to discount at the lower end, the confidence interval a response rate of 15% which means we'd have to hit 22%. Where we'd like to be obviously significantly higher than that based on our investigator-declared response. If we want to discount the response rate, the lower end of the comp is into 20%, then we'd have to hit around about 28%. So we should be in that ballpark. And should, therefore, be in a position to have a productive conversation about approval, a similar sort of response rate that Iovance, which has been approved then.

What's the median follow-up term that we should see for that data set?

Between 18 and 21 months.

And then the confirmatory trial, what does that look like? What's the sense of that.

Very similar population to the IGNYTE single-arm cohort second, third-line PD-1 failed melanoma. There's a reason why we run a single-arm study in the first place. It's not obvious what the control arm could be, and that still remains the case. Hence, the control arm will be a defined list of physicians choice.

Okay. Does that broaden the potential application of RP1 with that confirmatory trial?

It does not broaden the potential application node, but obviously, it's a randomized study and therefore, would be -- or should be approvable and reimbursable in Europe.

Got you. And the decision not to try and have a confirmatory trial that would broaden the label. What made -- what drove you down that path of similar?

When you look at confirmatory trial designs, you look at a number of different metrics, obviously, buying from the FDA probability of success. Whether you get a label in Europe and then also whether it can expand the label. But ultimately, we did not want to go for a frontline study. And we were somewhat constrained as much as the contribution of component of parts has to be part of the conversations as RP1 plus nivo. And nivo has to be somewhere there in the control arm. So when you look at all the constraints together, then actually having a study that could actually further broaden the label wasn't easily feasible.

When you start enrolling for that confirmatory trial?

We will start enrolling before the BLA filing in the second half where just start-up activities are underway.

Okay. Do you get a good sense of what substantially underway means?

They have not used that language. The language that we've used in our presentation is taken straight from the FDA minutes, which says underway.

Okay. So that just means like first patient in, you think or?

I presume so. It's underway. Yes.

Yes. And I guess, the recent approval that we've seen for Iovance and TIL therapy, does that change the commercial approach for you in any way?

No. I mean we're focused on our own commercial planning. We're not going to be limiting our commercial rollout to specialist centers or even academic centers. We plan to launch fairly quickly into the community. There's no reason why community physicians can't prescribe the product and treat patients, need a private room. We will provide clinical coordinators and training, and they can keep their patients. And otherwise, they probably lose their patients to a clinical trial and they can buy and build. So we've had a very different setup in terms of the technology and the side effect profile and will not be a similar launch strategy.

Does it in any way impact enrollment into the confirmatory trial? And/or does that matter? But -- just curious on your thoughts around if you have to plan around material therapy.

It may do at the margin. But I don't think it will be a sizable impact given the number of patients that can actually be treated with TILs based on Iovance is own forecast. And our study will also involve late-stage 3 patients and earlier-stage 4 patients. And ultimately, if, hopefully, the drug is approved, then we'll have to be recruiting quite heavily outside the U.S.

So that would be the one thing we should think about how the enrollment in that confirmatory trial potentially gets skewed in the U.S. with TIL therapy. There are some patients that will go TIL therapy versus your original RP1 trial.

Possibly, but I don't think there's much -- there's a terribly large overlap in terms of the proportion of melanoma patients at TILs is appropriate, too.

Okay. I mean -- I know what we [indiscernible], they kind of talked about TIL therapies maybe for most fitter patients and then RP1 could be for the less fit patients in the sense of that does has never really changed in that perspective. Do you kind of agree with that?

Yes, although I think it's slightly simplistic, and I think you have elderly patients that are not -- may not be eligible for TILs therapy given the toxicity profile. But also we'll be pursuing the labeling in things like adjuvant patients where TILs doesn't have a label. And I think given the involvement of the process and the toxicity that patients will -- yes, they have to be somewhat healthy, but at the same time to justify the process and the toxicity, you also have to be relatively late stage. So you're going to be late stage yet at the same time, robust enough to take the therapy. So over and all, it's is a subset of melanoma patients that can be potentially be pursued. And so there will be some overlap, but I don't think it's that significant an overlap.

The commercial infrastructure, where are you for building that? What do you need to add? And kind of what does that look like, I guess, as we exit the year?

We've been doing commercial planning now for a couple of years. We have our senior team in place. We have a Chief Commercial Officer. We have VP of pricing and market insights, VP of Analytics, we have VP of Sales. And we have a correct medical affairs team. We were in talks with the sales force until closer to BLA filing after a pre-BLA meeting. But all the high-level planning has been underway for quite some time. And we're just looking at the different archetypes of -- and ensuring that we can serve those archetypes needs, whether they be an academic center, whether it be a large rolled up commercial network or whether it's a bit more of a piecemeal -- community network or more piecemeal community centers. We believe that of the melanoma population, about 80% are going to have lesions that we can inject and that will split down between roughly half, i.e., 40% simple superficial injection, which can be done even by research analysis to the other half, which will require some kind of image guidance from simple ultrasound techniques to more sophisticated ultrasound or CT-guided techniques. Obviously, in the academic centers, that's all relatively straightforward. And in the community centers, they also have access to radiology as well, but there we may have to employ our own clinical coordinated team to sort of grease the wheels of the flow of patients, which will be under the care of the oncologists but may need to go a few back and forth to radiology a few times for their injections.

Appreciate that. Just the communication and I guess, what we should be listening for on conference calls between now and the BLA filing where you kind of signal if you've had like the pre-BLA meeting, et cetera.

Remains to be seen. We're going to sort of stay at a fairly high level on our guidance as we go through the year. We will be having a pre-BLA meeting. Obviously, that will be after we've got all the data and it's available to be included in a briefing book. What we quite say about when the meeting is or whether the meeting has happened, I can't answer at this point.

Got you. Okay. Perfect. And RP1 in CSCC and the CERPASS trial, is there a meeting with the FDA plan to discuss that data and the kind of the path forward?

There is not. We've set the data in, obviously, shortly around the time it was disclosed to the FDA. And we have no plans to meet with them at this point as we're not pursuing registration currently with CSCC, we're focused on getting our first approval where there's a clear line to where we need to be, which is in melanoma. In CSCC, we'll probably take a further data cut at some point. Not planned this year when we think data will be close to full maturity and then decide whether or not to have a conversation with the agency and/or see whether there's potential for compendia listing and some more provocative subsets within the main data set.

Okay. That would clearly be on 2025 kind of post approval or what you're thinking.

Yes. So it's not thinking more in that time frame than anything in the near term. Yes.

And there's no plans for another trial in CSCC.

There are no plans for another study in CSCC.

Okay. And then the solid organ transplant recipients of this kind of ARTACUS study. You've got data at AACR. What should we expect to see? What should we be honed in on?

Yes. So there's nothing new at AACR. It's just a resummary of what we disclosed late last year, which was a 35% response rate as monotherapy, and it's very difficult to treat patient populations. We actually had a KOL in the space come present to the whole company a month ago, not because we invited them to, they invited themselves. So I wanted to say what important work we were doing given these individuals really have had no options -- very limited options.

What's the path forward there? Would that be registrational study or NCCN guideline changes or?

We are having just that question -- conversation internally at the moment. It could be one or the other. I haven't definitively decided, I think, either way, we are going to reinitiate -- reinforce efforts to actually recruit more patients into the study. It Is an important study. It is an unmet need. And yes, it's an interesting dynamic too from a dosing standpoint. In all our other trials, we do 8 cycles of dosing and rely on the engender [indiscernible] systemic immune response to engender benefit thereafter. These patients, given they're immunosuppressed, then you have to rely more on the local effect of the virus to have benefit. And you really give more or less continual dosing. So it's slightly different in that respect. But it could lend itself to obviously having -- from a commercial perspective, having to give higher volumes.

Interesting. Yes. So the most obvious thing would be -- I mean, can it be added to NCCN guideline change? Or is it because of that dosing difference? Does that change?

That wouldn't change that dynamic, no. I mean just like anything for NCCN, you'd have to go in front of the Board and make the case for why it should be included in the guidelines from a risk/benefit perspective after -- obviously after 2 things. One thing is you -- first of all, you got to have your first approval and two, got to publish the data.

Got you. Okay. Perfect. And then RP2, RP3 and uveal melanoma, kind of plans there for the trial, how it initiates and what the benchmark is in your eyes?

So RP2 -- RP1, we still plan to establish a broad skin cancer franchise, RP2, we plan to establish a rare cancer franchise. We've seen very compelling monotherapy activity and really very difficult to treat tumors in the salvage setting, including [indiscernible], slightly growing cancer, chordoma, sarcoma and uveal melanoma. We've chosen uveal melanoma as a foundational study to get to a registration to establish this franchise. The actual design of our study, we're not quite yet ready to unveil. We are in discussions with the FDA around the design. We should be able to again speak to that in the second half with the idea to get to first patient in and around the end of the year.

Okay. And what's the benchmark for uveal melanoma?

Well, the bench -- the design we're working on, which will likely involve time-based endpoints, survival and PFS, but I can't really speak to what the benchmark is without describing the design, which we're not quite ready to do.

Okay. We can come back to you at any time in the second half?

You can.

[indiscernible] design. There's nothing kind of out the ordinary is not like you're not going to be doing it in combination, it would be a single agent.

We'll come back to the design.

Okay. And then the HCC trial as well, I guess, similar sort of questions of like where you're going to place that? And yes, where -- when does it -- remind us the status of the HCC trial and what it looks like and when we could see data?

Originally, we set up the HCC trial with RP3, but we discontinued RP3. So actually switching to do it now with RP2. So we haven't actually got the study underway, but should be underway at some point in the middle of the year with data in 2026.

Okay. And the benchmark and like how that fits into the treatment paradigm? Is it far more complex?

[indiscernible] in second, third-line HCC. So really seeing anything would be interesting [indiscernible] failures.

Got you. And I'd love to go back to -- in the last couple of minutes to go back to the kind of commercialization approach for RP1 and kind of how you think about the landscape, if it's TIL versus RP1 or if it's academic centers versus community settings?

Yes. As I say, probably a risk of repeating myself, I just don't think there's just that much overlap between the patient groups that we would be potentially competing for. I think we can potentially address up to 80% of the melanoma population and TILs is perhaps 1/4 of that number. Could there be some patients that will be sequenced TILs before an RP, possibly, but it remains kind of fact that RP1 has 90%, mainly Grade 1, 2 constitutional type symptoms and TILs has also 100% grade 3, 4 spattering of Grade 5. So from that perspective, it would be more logical in that subset where we might have a similar population to go after to sequence RP1 first, more from an efficacy standpoint, for RP1 did not put patients into some long-term durable remission, then theoretically, it could increase the number of T cell epitopes to harvest from TILs and potentially make receptivity to TILs even higher.

Got you. How should we think about pricing? Is it per dose -- and then the range you're kind of thinking about what are good comparables?

We'll probably go with the orthodox volume-based pricing or comparable to start with anti-PD-1, about 180 and go all the way up to [indiscernible] about 700. So -- those are probably 2 bookends. We're not going to give any further guidance on that. I do realize those bookends are quite large.

Perfectly narrowed it slightly through, yes. Thank you. That's great. Always a pleasure speaking to you.

Thank you, Peter.

Enjoy the rest of the conference.

You too.