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, you know, RP1 filing, relapsed, refractory melanoma, and kind of, we've got a series of other areas we'd like to cover as well with time. But first question really around the path to approval with RP1. You know, do you expect accelerated approval and off of this single-arm IGNYTE study? Yes. 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. 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. 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 one in three patients by way of durable response. It was an interim look at that registrational cohort, six months after 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, and that date was March the eighth, 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 Investigator-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. Gotcha. Is there... What's the risk as you go from independent review or investigator review to central review, as we think about ORR, CR rates, et cetera? Yeah. 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 then? Well, we put a lot of our original scans actually on our website. This, 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 there's 10% degradation of response. But as I said, not really expecting it to be anything material that would change the perception of the data. Gotcha. With the data you show in the second half, will that be central review, investigator? Will it be both- That will be central review as well. We won't present the data until it's been centrally reviewed from the official analysis. Gotcha. Okay. And there, there's no point in showing that investigator review 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. Yeah. Okay, perfect. Thank you. And then, are there any risks around delays, you know, 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 elucidating complete response is a lot more involved than elucidating simple response. So actually expecting this to be a relatively straightforward process. We'll start it in the spring and should be through it by midyear. What's the bar for accelerated approval in terms of ORR, CR, duration, and response we should be thinking about? Yeah. I mean, the FDA have never set no bright line in terms of what the bar is. We actually set up our protocol to discount at the lower end of the confidence interval a response rate of 15%, which means we'd have to hit 22%. Although 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, the confidence interval of 20%, then we'd have to hit around about 28%. So, you know, we should be in that ballpark and should therefore be in a position to have a productive conversation about approval. Similar sort of response rate that Amtagvi has just been approved on. ...What's the median follow-up time that we should see for that data set? So I'll say the median, maybe between 18 and 21 months. Okay, thank you. And then the confirmatory trial, what does that look like? What's the sense of that? A very similar population to the IGNYTE single-arm cohort, second, third line PD-1 failed melanoma. Yeah, 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 physician's choice. Okay. Does that broaden the potential application of RP1 with that confirmatory trial? It does not broaden the potential application, no. But obviously, it's a randomized study, and therefore, would be or should be approvable and reimbursable in Europe. Got you. But the decision not to try and have a confirmatory trial that would broaden the label, what drove you down that path of similar? When you look at confirmatory trial designs, you look at a number of different metrics, obviously, guidance from the FDA, probability of success, whether you get a label in Europe, and then, yeah, also whether it can expand the label. But ultimately, we did not want to go for a front-line study, and we were somewhat constrained as much as the contribution or 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. Got you. And when do 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, yeah. Yeah. Okay. Thank you. And, I guess, the recent approval that we've seen for Iovance with TIL therapy, does that change the commercial approach for you in any way? No. 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. They just need a, you know, private room. We will provide clinical coordinators and training, and they can keep their patients, and otherwise they'd probably lose their patients to a clinical trial, and they can buy and bill. So, we have a very different setup in terms of the technology and the side effect profile, and you know, it will not be a similar launch strategy. Got you. Did it in any way impact enrollment into the confirmatory trials and/or does that matter? But just curious on your thoughts around if you have to plan around the TIL 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's own forecast. And our study will, you know, also involve, you know, late stage three patients and earlier stage four patients. And yeah, ultimately, if hopefully the drug is approved, then we'll have to be recruiting quite heavily outside the US. Got you. 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 the TIL therapy. There are some patients who 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 that TILs is appropriate to. Okay. I mean, I know when we've done CAR-T work, 'cause they kind of talked about TIL therapy is maybe for the more fitter patients, and then RP1 could be for the less fit patients in a sense of that does- Uh- There's never really changed in that perspective. Is... Do you kind of agree with that? Yes, although I think it's slightly simplistic, then I think, yeah, elderly patients that are, you know, may not be eligible for TIL therapy given the toxicity profile. But also, you know, we'll be pursuing a label 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 you know, 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've got to be late stage, yet at the same time, robust enough to take the therapy. So-... Overall, it's a subset of melanoma patients that can potentially be pursued. So there will be some overlap, but I don't think it's that significant an overlap. Mm-hmm. The commercial infrastructure, where are you for building that? What do you need to add, and kind of what does that look like as, 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, you know, VP of Pricing and Market Insights, a VP of Analytics. We have a VP of Sales, and we have a crack medical affairs team. We won't drop in 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 that 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 gonna 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 nurses 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 all still have access to radiology as well, but there we may have to employ our own clinical coordinator team to sort of grease the wheels of the flow of patients, which will be under the care of the oncologist, but may need to go a few, you know, back and forth to radiology a few times for their injections. Gotcha. Thank you. Appreciate that. Just the communication and, you know, I guess, what we should be listening for on conference calls between now and the BLA filing. Will you kind of signal if you've had the pre-BLA meeting, et cetera? It remains to be seen. We're gonna sort of stay 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 can say about when the meeting is or whether the meeting's happened, I can't answer this at this point. Gotcha. Okay, perfect. Then, then RP1 and CSCC, and the CERPASS trial, is there a meeting with the FDA planned to discuss that data and the kind of the path forwards? There is not. We've sent the data in, obviously, shortly around the time that 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 a compendia listing in some more provocative subsets within the main dataset. Okay. That, that would clearly be on 2025, kind of, post-approval, you're thinking? Yes. Okay. At least I'm thinking more that timeframe than anything in the nearer term. Yeah. There's no plans for another trial in CSCC? There are no plans for another study in CSCC, no. Okay. And then the solid organ transplant recipients, so this kind of ARTACUS study, ARTACUS, ARTACUS study. ARCTICUS. Thank you. Yeah. You've got data at AACR. What should we expect to see? What should we be honed in on? Yes. I don't think there's nothing new at AACR. It's just a re-summary of what we disclosed late last year, which is a 35% response rate as monotherapy, and this is very difficult to treat patient population. We actually had a KOL in the space come present to the whole company a month ago, not 'cause we invited him to. He invited himself to, wanted to say what important work we were doing, given these individuals really have no options. Yeah ... very, 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. Haven't definitively decided. I think either way, we are going to reinitiate, you know, 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 eight cycles of dosing, and we rely on the. In general, we force systemic immune response to engender benefit thereafter. These patients, given they're immune suppressed, then you have to rely more on the local effect of the virus to have benefit, and you really give yeah, more or less, continual dosing. So it's slightly different in that respect, but it could lend itself to obviously having higher volumes. Interesting. But yeah, so the most obvious thing would be, I mean, can it be added to an NCCN guideline change, or is it because of that dosing difference, does that change the dynamic? No, 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 two things. One thing is, first of all, you've got to have your first approval, and two, you've got to publish the data. Gotcha. Okay, perfect. And then RP2, RP3, Uveal Melanoma. Kind of plans there for the trial, how it initiates, and what the benchmark is in your eyes? So RP2, like 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 in really very difficult to treat tumors in a salvage setting, including esophageal, salivary gland cancer, chordoma, sarcoma, and uveal melanoma. And 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, but should be able to again speak to that in the second half with the idea to get a first patient in around the end of the year. Okay. What's the benchmark for you for uveal melanoma? Well, the design we're working on, it should 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. So we can come back to you in- Yeah. Sometime in the second half. You can. Trial design. But there, there's nothing kind of out of the ordinary. It's not like you're not gonna be doing it in combination. It'll be a single agent. We'll come back to the design. Okay. And then the HCC trial as well, I guess, you know, similar set of questions of, like, where are you gonna place that? And, yeah, where does it remind us the status of the HCC trial of what it looks like and when we could see data. Well, originally, we set up the HCC trial with RP3, but we've discontinued RP3, so we're 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. The benchmark and, like, how that fits into the treatment paradigm? Yeah. It's far more complex. This is in second- and third-line HCC, so really seeing anything would be interesting, seeing the Atezo/Bev failures. Gotcha. I'd, I'd love to go back to the... in the last couple of minutes, go back to the kind of commercialization approach with RP1 and kind of how you think about the landscape, you know, if it's TIL versus RP1 or if it's academic centers versus community settings. Yeah. As I say, probably at 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, you know, perhaps a quarter of that number. Could there be some patients that would be sequenced TILs before an RP? Possibly, but it remains a kind of fact that RP1 has 90% mainly grade one to constitutional-type symptoms, and TILs has almost 100% grade three, four, and a spattering of grade five. 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. Moreover, from an efficacy standpoint, if 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. So- Gotcha. How should we think about pricing? Is it per dose? And then the range you're kind of thinking about, what are good comparables? Yeah, we'll probably go with the orthodox, volume-based, pricing. Or comparables start with anti-PD-1, about $180, and go all the way up to, Kimmtrak at about $700. So, those are probably the two bookends. We're not gonna give any, any further guidance on that at this point in time. I do realize those bookends are quite large, but- Perfectly. So you've narrowed it slightly for us. Yeah. Thank you. No, it's great. Always a pleasure speaking to you. Thank you, sir. Enjoy the rest of the conference. You too.