All right, great. Well, welcome to the Fireside Chat with Immunocore. I'm pleased to welcome Ralph Torbay, Chief Commercial Officer for the discussion. Ralph, welcome. Thanks for joining us. Michael, thank you very much for having me, and thank you to Guggenheim for having us today. So maybe just diving right into Q&A, starting out with Kimmtrak, which has been a strong commercial performer in uveal melanoma and recently reported, again, growth in the third quarter. And I think you've commented before that you think the product has now a 60% penetration in a frontline setting. Yeah, but talk about perhaps a little bit market dynamics in uveal melanoma and how much, where you see sources of additional growth as we think about 2025, especially. Sure. No, thank you for that question. So when you think a little bit about where we've come from, so this is our 10th quarter of growth since launch. So performance has been very good. Year to date, we have $226 million in sales. That's a 32% growth versus the same period last year. And as you commented, our market share is roughly around 65% penetration in the U.S., a little bit higher in countries outside of the U.S. And really, I think that there's still growth to be had. This is a period of difficult next steps because we're growing into the community, and this is lower density of patients in the accounts. And the good news there is actually that we have half of our new patient starts are in the community. So clearly, the adoption has been very strong. There's still opportunity to grow. So I'd expect incremental growth to come from the US moving forward. Okay, and then, yeah, as you mentioned, the product actually has a very strong ex-US sales contribution. Can you just comment on market dynamics ex-US, especially in Europe, and how we should think about the evolution of that market? We've launched in 11 countries to date. Most of them are in Europe. And that has driven a lot of the growth, ex-US. Penetration has been very good. We're standard of care in most countries where we've launched. The ones where we're not yet standard of care are basically we've not had enough time from the time of reimbursement to establishment. Market shares are very high. Like, for instance, in Germany, it's over 80%. Similarly, in France, duration of therapy is also trending up in a lot of these countries now at 11-plus months. So we're getting good compounding wins from DOT and good penetration. We expect, actually, in Q4, a launch in Poland. And potentially next year, we're finalizing our agreements with the UK. So that could be a launch. Overall, I think because of pricing dynamics, you can expect this to be incremental to really the growth that we see in the U.S. Okay, great. And then as you think about label extension opportunities for Kimmtrak, just remind us how you think about the opportunity in cutaneous melanoma. So I'm very excited about that opportunity in cutaneous melanoma. So taking a step back and to the reasons to believe for this opportunity, we had a phase 2 study in combination with checkpoint inhibitors where we saw a 12-month overall survival milestone of 75%. And if you compare this to historical, around 55%, it's obviously very impressive. So I think about the study as a study that's de-risked because we have safety in combination with checkpoints, and we have efficacy, albeit in, well, in the same setting in 60 patients, so not as large of a comparative population. The TEBE-AM study enrollment is going very well. We're on track to finish enrollment in the first half of 2026. This is an event-driven study. So we expect the second half of 2026, we would be seeing data, and then potentially launch in the first half of 2027. Now, when you think about the second-line plus cutaneous melanoma setting, this is about 2,000-4,000 patients, so 2,000-4,000 times the size of the uveal melanoma population. We expect to be able to keep our pricing or carry our pricing from uveal. And the reason for that is because it's a high unmet need population. We have an overall survival endpoint in our study. And when you also think about the competitive edge, I guess, that Kimmtrak could have, not only uveal melanoma treaters treat also cutaneous melanoma. So they have familiarity with the product. In addition to that, a lot of the other modalities in that setting, such as TILs, they're not off the shelf. There's a little bit more complication. And it's a different set of population. So I think Kimmtrak could be very competitive in that setting. Okay, great, and so, yeah, maybe then shifting gears to some of the pipeline programs, starting with PRAME, where we've seen data earlier this year in ovarian cancer and also in melanoma. I think response rates have been modest, but you've obviously advanced in melanoma, and maybe if we step back, what are your latest thoughts on the PRAME program and where else it could go beyond melanoma? So I think that there are several places where it could go from an expression perspective, as well as from reasons to believe in the, I guess, T cell PD-1 axis. And those are some of the areas where we're at, which is non-small cell lung cancer, as a for instance. Ovarian cancer, well, it's less responsive to checkpoint inhibitors. There, PRAME expression is very high. And we believe that there's also reasons to believe that potentially combination of PRAME has a path forward. So I think cutaneous melanoma, non-small cell lung cancer, and ovarian cancer are really the areas where we're focused on right now. I think there's been some debate on some of the phase 1 data, especially the response rates were quite low, similar to, I guess, what you've seen originally with Kimmtrak. The question has been, so what gives us confidence that the profile could translate into long-term improved outcomes on long-term endpoints like PFS or OS, which is obviously what you evaluate in phase 3 melanoma, for example? I think the first proof of confidence is the fact that even with Kimmtrak, we see a hazard ratio of 0.7 in PFS. PFS is that thing. Obviously, the 0.5 overall survival hazard ratio, which is, I think, what everybody recognizes as a value for Kimmtrak. With PRAME, with brenetafusp, we see some of the similar hallmarks of closed umbrella, which means that disease control rates are durable. The responses are durable. We see a disease control rate in late-line melanoma of roughly 56%. Interestingly, when you compare that to the Opdualag response rate or DCR of around 40%, obviously compares favorably with all the caveats of cross-trial comparisons. That's been really the reason why we took the step of advancing into first-line cutaneous melanoma, because we saw the Opdualag combination, so that's Nivo plus LAG-3, and then the monotherapy data for PRAME. We thought that, look, if you're going to earlier line where potentially T cell fitness might be higher, and in addition, you combine with nivolumab, there's a good chance that you could beat what is currently the standard of care, which is either a nivo monotherapy or Opdualag. Okay. And then, yes, we have seen data as well in ovarian and ESMO. And yeah, just talk about what are potential next steps in ovarian cancer, and what are your latest thoughts on that particular opportunity? So there, we also believe that the product is active, right, and that there's a path forward. So we see also in monotherapy disease control rates of around 58%. And then we see also around 68% in combination. Interestingly, these are very heavily pretreated patients, which makes the disease control rate even more important. And in combination, we've actually presented data at ESMO where we've shown that some of the chemotherapy can induce an expression of peptide-HLA, which we believe could be synergistic with our platform. So in terms of next steps, what we're looking for is really expansion of the platinum refractory ovarian cancer combinations, and then looking at earlier lines where potentially you could presume less aggressive disease and higher T cell fitness in the platinum-sensitive setting, and going into combinations there as well. Okay. And then what are your latest thoughts on lung cancer opportunity? Lung cancer is an interesting opportunity because, as we discussed, this is a place where T cells have had a big role. Checkpoint inhibitors are first-line center of care for a lot of patients. This is also a disease where there's a lot of complexity. It's very heterogeneous, whether it's mutational drivers or the disease itself. Patients can be heavily pretreated. A lot of the phase one patients come to your trials after three, four lines of treatment. It's a very heterogeneous disease. It's a disease that in late lines is very aggressive. In fact, RKOLs tell us it's very different from what you see in earlier lines. In conversations with KOLs, they've all said, look, it's very important for you to interrogate properly the subsets in this disease, whether that be through combinations, earlier treatment, really just asking the questions that will enable you to really decipher if there's a subset and what that subset is where you can move forward. In fact, they keep mentioning the example of ADCs, where even ADCs, which have had a fairly straight path forward in a lot of other diseases, in lung cancer, they could have saved a lot of money in these companies if they had interrogated better some of the subsets. Okay, so specifically in the lung cancer cohort, what are sort of the next steps for that particular evaluation? So some of the next steps that we're considering is combination therapy, earlier line of treatment. So we have a combination, for instance, with osimertinib. So upon progression of osimertinib, you add PRAME, and then we look at the dynamics of the response. I think it's a great place to look for signal because of the fact that generally EGFR-positive patients are insensitive to checkpoints, so big unmet need. And in addition to that, they tend to be younger and presumably more T cell fit. So it's a great place to see a little bit of the immune component while the unmet need remains very high. Right. That's a good segue to my next question. I know David has talked about this T cell fitness signature that you've been looking at in a post-hoc way in some of the studies. So is that something that you're planning to leverage in development as a sort of prospective screening tool in any way? So we have to go back to the genesis of the T cell fitness, which when you look at our platform, which is basically T cell engagers, so we bring T cells from circulating blood. We bring them to the tumor in the hopes that it would identify the tumor and kill them. So presumably, the T cell fitness or the immune fitness is relevant and important to that algorithm. So what we've done is we've looked at the Kimmtrak data initially, and we saw a three-gene signature that correlates with T cell fitness. And we saw that in patients that were more T cell fit, and we used medians to determine high, low T cell fitness. We saw in patients who were high T cell fit that there was an improvement in overall response in PFS, in overall survival. Then we looked at the same three-gene signature with the brenetafusp data, and we noticed the same thing. So then the question was, okay, do you use it prospectively, or do you use it to select patients somehow? And I think the answer to that is we don't use it as a diagnostic to select patients because all patients across the board benefit. These patients just happen to benefit more. But what it helps with is to select, for instance, diseases or lines of therapy where you think T cell fitness will be higher. So an example, as we discussed, is EGFR patients. But it's also like first line in cutaneous melanoma or first line in ovarian cancer. These are places where we presume T cell fitness would be higher. Right. And so if we step back, so what are the next updates, the next public disclosures that you're planning on to do on the PRAME program? So on the PRAME program more broadly, so we're currently working on, as we discussed, expanding our platinum-sensitive and platinum refractory ovarian cancer enrollments. We're also interrogating the non-small cell lung cancer patient populations. And we have our PRAME-HLE, actually, that we plan to enroll the first patient by Q4 of this year. And overall, we have our PRISM-MEL study, which is where a lot of our focus is in enrolling that study fast. On the half-life extended PRAME molecule, are there learnings from the initial experience, clinical experience, and how are they being incorporated in the clinical development program of the HLE program? It's a great question because the HLE program or the HLE molecule, it's actually very similar to the brenetafusp molecule in the sense that the TCR targeting arm and the CD3 are the same. We only added the Fc for half-life extension. Presumably, a lot of the learnings that we are deriving from the brenetafusp program will apply to the HLE molecule. Have you disclosed? I know it's early, but what cohort or what indications you're planning to evaluate in the phase 1 study? So we're first thinking about the fact, what is HLE going to provide to patients? So initially, the base case is it will likely help with convenience. Currently, a lot of the HLEs are being dosed on an every other week basis. Then, obviously, there's an upside that you could consider that it might help with efficacy as well. So first, we have to interrogate which one is it. Are we going to see more convenience? Are we going to see more efficacy? And then where is it best used? I mean, PRAME in the first-line PRISM-MEL study, it's actually well-positioned because it's a schedule where we start weekly, then we go every other week, and then we go monthly. So it's still a convenient schedule for patients. However, if you were to go into earlier, say, the adjuvant setting, cutaneous melanoma, or say, in lung cancer in earlier settings, then you would need an HLE molecule potentially for convenience, so it's really something that can open more doors for us if it's convenience, and if it's efficacy, obviously opens even further more doors. It sounds like maybe a tendency to move into even earlier stage patients with the HLE program. Potentially, yes. Great. And then, yeah, question on your infectious disease program. I know there's studies ongoing in HIV and hepatitis B, where I think you've guided to disclosing some early HIV data soon. And so can you just talk about the program in general and then sort of the scope of that initial data disclosure? So today, HIV is being treated really with a goal of disease control with antiretroviral therapy. I think the goal that everybody has with most of these diseases is eradication of the disease. So this is what we are trying to invest in. It's basically how do we get to functional cure. And the reason we believe our platform could potentially get us there is because a lot of the reason why patients recur is because of this reservoir of viral reservoir that exists in T cells. And because this reservoir, for the most part, is either virus that's incompetent, so not really expressing anything, or dormant, the expression on the cell surface is not, we don't believe, as such that potentially other modalities can get to it. However, with our ImmTAV, we've shown that we can kill at 10 copies or 10 proteins peptide-HLA expressed per cell. So we believe we can get to that level where we could potentially reduce the reservoir or eliminate the reservoir in HIV. And now, the way that you look at this in the clinic, and this is what our clinical trial are, we started with single ascending dose. Now we're going into multiple ascending doses. And that's what we expect to read out in Q1 of next year is 15 patients, roughly, from our multiple ascending dose study. And there, what we're looking at is we're dosing our ImmTAV in combination with ART for 12 weeks. Then we're stopping treatment. And then we're looking for the time to recurrence. Based on historical studies, we see that it takes on median two weeks for patients to recur. And by eight weeks, 96% of patients would have recurred. So if we can shift that in any way clinically with the addition of our ImmTAV, then that tells us that there's a chance that we can take a first big step towards that functional cure idea. And so if you can indeed demonstrate a delay in recurrence, what would future or next steps look like or next trials that you could undertake? So this being, I mean, if we can demonstrate this, this would be, I think, very important for the field, obviously, because no therapy has demonstrated this in the past. And significantly, obviously, it's about making sure that what we're seeing is reproducible. So presumably, it's a phase two at a dose that we believe to be clinically active and potentially with a control arm. So I think that would be an interesting next step. And then from there, you can think about all the potential avenues where this could go because I don't think the field has had something that really has impacted the reservoir in a long time. Okay. And then just in terms of potential relative to ART, which is used widely at this point, so how do you think about the commercial potential of this? So it's hard for me to conceive currently of the commercial potential. And really, the reason for that is because I don't think we've, I mean, other than looking across other infectious diseases that have had functional cure, and obviously, you've seen the commercial potential of those. But I still think that we're in early steps. However, even stopping ART is, I think, critically important for patients because these are therapies that, while have been a leap forward for patients, they still have side effects. They still have contraindications of pregnancy and other aspects of this. So it's still a burden on patients to be taking these therapies. So even the ability to stop for a while is not only from a payer perspective, it's good, you're curbing cost, but from a patient perspective, it's less side effects and potential things that you couldn't have done otherwise. Okay. And then I just wanted to ask a question about your PIWIL1 program, which is now in phase one as well. So going back to cancer. Yeah, just talk about the clinical development strategy for that product candidate and also any learnings, perhaps, from the PRAME program and how those could be incorporated into the PIWIL1 program. So that's exactly what we're doing. We're taking the learnings from the PRAME program and Kimmtrak and incorporating it into accelerating the PIWIL1 program. This is obviously our first in class, maybe only in class. I'm not aware of any other PIWIL1. And it's expressed in colorectal. It's expressed in colorectal, which is a tumor that is immune insensitive at this point and with a huge unmet need, roughly around 35,000 patients between GI and colorectal cancers with very poor outcomes. And interestingly, PIWIL is a poor prognostic factor in colorectal, which means that we believe it's going to be more conserved because the tumor relies on this pathway to proliferate. So the expectations there is we're dosing our first patient by the end of this year and/or we plan to dose our first patient by the end of this year. Expectations is to move as fast as we can into the dose finding. Right. And so, I mean, colorectal is also notorious for drugs, for response rate not being a predictive outcome in any way, especially when we look at standard of care. And so, yeah, what are some of the metrics that you're assessing in early phase one and perhaps phase two studies even to sort of give you confidence in the potential of PIWIL1? One of the things that we learned from the brenetafusp program and the KIMMTRAK program is that you have to look at different measures. What we call the hallmarks of our platform today in oncology, which is look at disease control rate, not just response rate. Look at the spider plot. Do you see that closed umbrella shape, which means that your responses are durable? Look at molecular responses with ctDNA because that could be a good indicator of what's going on in the tumor. Importantly, also look at combinations. Don't just focus on late line patients where the signal might be dimmed. Let's take a look at combinations early on. Not only that gives you a path forward, but also it enables you to have access to patients and disease that's probably more controlled. Great. Well, with that, Ralph, I think it's time to wrap up. So next up, we'll get the.