Okay, good morning, everyone. Welcome to Day Three of the Cantor Healthcare Conference. My name is Eric Schmidt. I'm one of the analysts at the firm, and it's my distinct pleasure to welcome back to the Cantor Conference Immunocore Holdings. Delighted to have with us today the company's Head of Research and Development, Dr. David Berman, and also the company's Head of Commercial, Ralph Torbay. I think we may have the Immunocore IR team somewhere in the audience as well. Can you not hear me? Better? Okay, great. Let's get right into it. David, maybe just, or Ralph, whoever would like to start with the high-level comments, just a quick two-minute overview on sort of the state of affairs of the company. Sure, Eric. First of all, thanks for inviting us here today. Immunocore is an incredible company. We invented the science of soluble T-cell receptors, and then we took that all the way to the first ever approved T-cell receptor, which was KIMMTRAK. That demonstrated a survival benefit. It was also the first time any T-cell engager has shown a survival benefit in a solid tumor, and it was the first time a survival benefit has been seen in uveal melanoma, which is the type of melanoma where checkpoint inhibitors don't work, indicating that we act differently from checkpoint inhibitors. Ralph's team has done a great job with commercialization. We can talk about that later. We have three lifecycle management phase 3 trials, two lifecycle management phase 3 trials for KIMMTRAK, and we can talk about TEBE-AM, which is the nearest term one, as well as an adjuvant. We have a phase 3 for the PRAME in first-line cutaneous melanoma. Finally, we've taken this technology, and we believe it can apply not only to oncology, but also to HIV and HPV, and interestingly, also for autoimmune. We have adapted this platform now for three therapeutic areas, and we have some interesting data that will be emerging over the next 12 months. Great. Let's start with the stock. This may be an unfair question for a Head of Research or a Head of Commercial, but shares have been fairly stagnant over the last year or so. You've continued to grow and exceed, to some extent, expectations on KIMMTRAK. It's now doing a $400 million run rate. I think your total enterprise value of the company is only about $1 billion. At least it's our assertion that you're undervalued. I assume you're going to agree with that. What is it that investors are not getting, in your opinion? Each of you spent a lot of time with us. Eric, thank you for the question. It's a very fair question, and I think what people maybe are not seeing is the potential of 2026. It's a very data-rich year for us. Specifically, on top of that data is going to be hopefully TEBE-AM, which could be a 2,000- 4,000 patient opportunity for KIMMTRAK. You know, it's a lifecycle management trial, you know, a high probability of success. We have phase 1/2 data that is very promising as well. I think 2026 can be a very significant year for Immunocore. Okay, we're definitely going to talk about TEBE-AM and the opportunity in cutaneous melanoma. In addition to that readout, what other things do you need to execute on in the next, say, 12 months or so in order to make this company successful? Eric, I think number one, we need to continue with the excellent commercial execution globally. That's number one that we have to do. Two is we have to execute on these phase 3 trials, notably TEBE-AM, which is near term. As you mentioned, we can talk about that more. I think the third thing we need to do is to deliver over the next 12 months data to inform the next steps for our earlier stage programs. For PRAME, probably in ovarian, for PIWIL1, for HIV, and then, of course, we're also having an autoimmune franchise, but that's a little bit later. I think the next, as Ralph said, 2026 will be an important year. Okay, let's briefly touch at least on the KIMMTRAK commercial outlook. It's been an amazing past year or two of delivery. Congrats, Ralph, and your team on that. Where do we stand in terms of median duration of therapy? I think that's been the number one driver of adoption. How much longer can we see median duration continue to excel? Eric, I mean, it's a great question, mostly because the answer is I don't know. This is a first for me. You know, it's rare to see a medicine that does much better in the real world than it does in clinical trials. This is what we're seeing with KIMMTRAK, where the mean duration of therapy is 13 months at this point, which has exceeded what we've seen in the follow-ups at that point. Where is it going to go? I can't tell you now, but what I can tell you is that we hear two things. One is we meet patients who have been on therapy for seven years, which is very rare in this disease. Importantly, we meet physicians who tell us that they have patients alive that wouldn't be alive had they not received KIMMTRAK. It's quite transformational for a lot of people. Can you share in Europe where you're at with the duration of therapy, given the more recent launches? Sure. Interestingly, it's fairly consistent. Whenever we see treatment beyond progression being done consistently and the belief being high, we do see the duration of therapy follow, of course, right? In Europe, there are countries like France, for instance, where it's doing very well, and there's a lot of centralized healthcare there. We have physicians that are following up patients very closely. In other countries like Germany and so on, which are a little bit further behind but are still doing very well from a mean duration of therapy. One of the things that you shared, which does seem quite interesting, particularly for community uptake and then for the TEBE-AM potential, is reducing the 16-hour stay requirement. David, can you tell us what's going after the first three doses? Can you tell us how that may evolve over time? Yeah, so the 16-hour was sort of baked in 10 years ago when we started the trial. We didn't really know what the right overnight monitoring period is, but we certainly have lots of real-world evidence now that people can shorten the observation period. We are investigating very heavily a risk-based plan to determine who needs to stay overnight versus who doesn't. More to come on that, but we've certainly also baked in those learnings to our earlier programs so that we can try to avoid as much as possible the 18 hours. One more on KIMMTRAK in the commercial context. Could you just share with us how long you expect to maintain exclusivity? Our composition of matter patent is until 2030, and we have filed for an extension, which should extend it to 2035. One last one for me on the commercial. A skeptic might say that patients are staying on KIMMTRAK because there's nothing else, and I think that's to some extent true. We may get competition. It may not be as well established in terms of its efficacy parameters as KIMMTRAK, but do you expect, as newer drugs come to uveal melanoma, that we'll see some shortening in duration? Of course, you know, we have to wait and see. However, this is a disease of the liver, which, you know, when it progresses, it can be very problematic for the patient. We're often told that it's not that patients are feeling better, yes. In general, they're looking better as well. Specifically, no one would keep a patient on therapy if they weren't doing well, right? Especially with a disease such as this one that's in the liver. I do think it's a real phenomenon. It's not just something that, because we're lacking a second line. Eric, sorry, I just wanted to add another example to support what Ralph said, and we'll talk more about brenetafusp PRAME later. In the brenetafusp PRAME ovarian, where there are lots of other clinical trials and options available, we found over half the patients who have progression remain that investigators keep them on brenetafusp even after, suggesting that they believe they're still having benefit. Once again, radiologic progression does not mean lack of benefit, I think, with this platform. For sure. How do you sort of strengthen that messaging, or maybe you're already doing it commercially? What is the opportunity for you to take those anecdotes or those observations and codify it into some kind of a game plan for competition? We're lucky, and David and his team did a phenomenal job in that we're the first therapy in Europe, I believe, that has treatment beyond progression in the label. We've been thinking about this for a long time, and obviously, we've made sure that it's something that we can speak about from a commercial setting perspective. I think it's more publishing data, right? Part of the data rich year in 2026 is going to be some real-world evidence that we'll be publishing, and hopefully, we'll be linking some of this treatment beyond progression to overall survival. You want to go on? Sure. Let's move on to TEBE-AM in second-line cutaneous melanoma. Can you remind us of the study design here and the timing when we might see data? Yeah, so that's our nearest term phase 3. Patients who've progressed on PD-1, ipilimumab, and if they're BRAF mutant, BRAF inhibitors, are randomized to KIMMTRAK alone. KIMMTRAK monotherapy or essentially investigator's choice. They can get whatever they want. The primary endpoint is overall survival. That plays to the strength of KIMMTRAK. The trial is accruing well, and we expect to complete accrual in the first half of next year. Events, obviously, it's always event dependent, the primary analysis, but it could be in the second half of next year. Towards the end of this year, early next year, we'll be able to refine that cone of uncertainty and kind of better predict when the primary analysis can occur. These are later line patients, so there's not a lot of good options left in that control arm. What are you expecting to see in terms of the control arm survival? Yeah, Imogen, in terms of the control arm survival, we're expecting, I use a one-year survival rate of 55%, which is a median probably of 13 months or so. I get that from lots of different observational and clinical trials in that setting. It seems to be rock hard at 55%. Even the TILs data has a one-year survival of 55%. there anything you can share on what those patients are getting in the control arm? Based on the eligibility criteria, we've done some real-world evidence analysis of what people like this would get, and we estimate about 1/3 usually get PD-1 retreatment of some form, even though we know that there's no benefit. People also get re-challenged with targeted therapies if they're BRAF mutants. Some get chemotherapy, and then, of course, clinical trials have some Venn diagram overlap with that. We expect our trial to mimic what we see in the real world. You already referenced the phase 1/2 data, David, that support this study. What are the reasons, and you can recap that data for us if you'd like, but what are the reasons to believe this could be successful? Yeah, so a couple. One, just based on the tumor. It's melanoma, and it expresses GP100, very similar to uveal melanoma. The expression levels are roughly the same or high enough for us. That's number one. Number two is in our initial phase 1 trial, which was done over a decade ago before PD-1s were really used, we got some patients who are essentially PD-1 naive. In that population, the one-year survival was 75%. It was a small phase 1, but that's the one-year survival for nivo and pembro. It suggests as a monotherapy, that survival benefit could be there. We had the checkpoint combination in patients who were PD-1 prior treated, and there, the one-year survival, interestingly, was also about 75%. Those were the initial reasons to believe. We've also done a deeper dive in that checkpoint combination trial, and we see many of the same surrogates of benefits, tumor reduction, kind of pseudoprogression, durable tumor reduction. We see that same data in the cutaneous as we see in uveal. To us, same GP100 melanoma, promising survival, similar surrogate metrics that we saw for KIMMTRAK and uveal. That's our reason to believe. These patients, unfortunately, don't have particularly long survival. Based on that, when are you expecting to see data? What we can predict better is the accrual, which is probably the first half. In terms of data, right now, there's kind of a wide cone of uncertainty. It could be the first, it could be the second half of 2026, sorry, second half of 2026. Later this year, early next year, as the events get more mature, we can refine that cone and better predict when the primary is likely to occur. How many events are you looking for? Eric, we haven't really talked about the statistical analysis plan. That's just been my historical preference. Is there anything different from this study relative to, I don't know, other cancer trials? Yeah, okay. That's a good way to put it. I would say probably not. You know, it's, in my mind, a routine well-powered overall survival trial in cutaneous melanoma. Remind us, did you have an interim analysis or is that planned? Yeah, we haven't also talked about that. You know, it's a routine survival trial in cutaneous melanoma is how I would phrase it. To 55%. Is that something maybe we should think about when we were thinking about that? Yeah, so the question, just in case they couldn't hear it, is, is the powering assumption we should assume the 75% that we saw for KIMMTRAK versus the 55% historical. I mean, that's our reason to believe. I would never power a study with that delta because, you know, you always get some type of regression somewhere. That's our reason to believe. In terms of powering, what I would say is, for me, a survival late line trial in cutaneous melanoma should have a hazard ratio in the low 0.7 range to be clinically meaningful. I think 0.8s to high 0.7s has less clinical significance to me. You mentioned a pretty barren landscape in the second line plus cutaneous melanoma. What are the potential competitive therapies that you might need to compete against today? I'm thinking TILs and maybe others are coming or not. I don't know. How do you see this as a commercial opportunity? It is a very important opportunity because there's a high unmet need for patients here. Even though they have TILs today, it's a very specific type of patient that can get TILs. The process of TILs or even TCRTs or other therapies involves a whole chemoablation and it's a long and arduous therapy. Whereas this is off the shelf, potentially the first one with an overall survival endpoint that we can talk about, and really one that a lot of these melanoma physicians are experienced with, right? They're using it in uveal melanoma. About 50% of physicians have experience with KIMMTRAK today, actually. I guess on that, how do you view the need or shifting needs of your sales force, if there are any, when you expand into cutaneous melanoma? I think it's about making sure that we are able to go after physicians who are treating cutaneous melanoma. Cutaneous melanoma is one of the diseases that is often treated in the community. 70% of treatment happens in the community. There is an expansion to be seen, of course. That being said, I think it's just additive to what we have, not really quite a whole other line. One of the things we've been pleasantly seeing is about half of all cutaneous melanoma treaters in the U.S. have experience with KIMMTRAK. That's a helpful fact. What do you make of the big guns that might be coming behind you, the cell therapies that are out there also targeting the same HLA-A2 population? Yeah, I consider KIMMTRAK a big gun also, but I think that there's going to be room for cell therapies. I think definitely they have demonstrated, especially in melanoma, whether it's TILs or whether it's TCRT, I think there's a place for that. I think a couple of things. One is we're going to launch, if it's positive, with overall survival. TILs launched with response rate under accelerated approval and a PFS confirmatory trial. RP1, I mean, TCRT, RP1, the TCRTs, because you asked about cell therapy. TCRTs is going to launch with a PFS. I think there's going to be just different populations. I think the strength of the data will guide who gets what. When you have that data, how long would it take for an NCCN listing? There's an interesting change in guidance from, not change, but, you know, different guidance from the FDA, which actually now enables us to put medicines in the commercial space. Once you have data, shortly after that, basically, you can start promoting from a company perspective, both commercial teams and medical teams on that data, provided it's robust enough and so on. NCCN becomes now one of the key aspects that we have to focus on to make sure that then there's reimbursement even before approval. Usually, depending on when the data gets presented, they tend to meet once or twice a year. I think in this type of setting where the unmet need is so high, potentially it could be a separate meeting after the data, if the data is positive. If we get data in 2026, and it could be first half, I assume. You said second half. Go ahead. No, no. It can't be first half. It can't be first half because, you know, it can't be first half. I'll just put it that way. No, because we don't want to do any type of analysis until we've completed randomization. That's going to happen in the first half. Yes, yes. Why couldn't it be soon thereafter? It could, but it's unlikely. Okay. Let's say the data come out the second half of next year. Within a quarter or two, we could start to see sales impacted. Is it that quick? If there's a, yeah? It could be that quick. Yes. I think the key rate-limiting factor would be some type of publication that can be used by a sales force, you know, a peer-reviewed publication. That's more than a conference abstract or a presentation? It's usually preferable to have a publication in the setting. Also, I mean, I think this is significant enough that there would be a lot of interest in it. How long would the publication take? How long can David write? Yeah, now keep in mind that David sees the data a little bit before everybody else. The team, of course, is working on a lot of this before the conference. Can you type quickly? Yeah, no, that's, there'll be a lot of excitement. Should we move on to Prism? Yeah, let's talk about brenetafusp and the PRAME program in first-line cutaneous melanoma. David, investors didn't love the data at ASCO last year. What do you see that they don't? Yeah, so, you know, when I joined the company seven years ago, I looked at the phase 1/2 data for KIMMTRAK. I said, you know, in my experience, and I've been working in melanoma 20 years now, started at BMS. In my experience, this is a real drug, and I believe it's going to have a survival endpoint. A lot of people didn't believe that because the response rate was low. I'm using the same type of principles in my experience that I then, of course, we then took to investigators and health advisors, not just me alone. These are the things that swayed me. Number one is we have monotherapy activity for brenetafusp alone in late-line cutaneous melanoma, and you can benchmark that. Although it's difficult to find LAG-3 monotherapy data, to me, the brenetafusp data, it's more active than LAG-3 monotherapy, and it has better disease control than LAG-3 plus PD-1, RELA-020, in a similar population. That's point number one. Point number two is we have done translational studies to show that as you move into earlier lines, you get better T-cell fitness. Excuse me, you get better T-cell fitness. We believe when we move into first-line, brenetafusp should have even more activity. The third factor is in first-line, we are now combining two agents, nivolumab and brenetafusp. Each of them have separate monotherapy activity, and we're going against nivolumab monotherapy. It's an add-on versus NIVO mono, and it's an add-on versus NIVO plus LAG-3. Once again, in my interpretation, brenetafusp monotherapy is even, you know, cross-trial, but it's more promising than NIVO plus LAG-3. That's the reason for me to believe. We took the, it's not just me, obviously, but we took it to KOLs worldwide, and they signed on. We have good accrual now, and we're on track for the dose selection later this year. Remind us of that phase 3 design, the timing of the study, and then the different doses that you mentioned in the dose selection process. Yeah, so the design actually anticipated NIVO plus LAG-3 because we knew, obviously, it was already approved, but we knew that in the U.S., you have to be better. It's first-line patients, standard first-line patients are randomized to NIVO plus brenetafusp on the experimental arm, versus in the U.S. and a few other countries, NIVO plus LAG-3, because we want to have some evidence that we're superior. Otherwise, how are we going to displace NIVO plus LAG-3? In the rest of the world, it's going to be nivolumab monotherapy. The control arm will essentially be a blend between NIVO and NIVO LAG-3, a minority NIVO LAG-3. The trial does have two initial doses in the first 90 patients or so, and an IDMC will select which one of those doses to continue. We think the trial should be about a three-year trial, but we need to refine that once we get up to steady state accrual. Remind us the expectations for the number of patients that are going to be in the U.S., or is it New Zealand or the other country that has approved? Yeah, so it's Australia, the U.K., Canada has it, and it's approved in all comers, not just approved in a subset. In the U.S., historically, it's been about 10% in melanoma trials from the U.S., but we will expect to have more NIVO LAG-3 than that. We haven't decided exactly the number. We have a statistical target number that we can draw inferences from, but we haven't yet decided exactly. Right now, we say a minority will be NIVO plus LAG-3. As we think about the commercial opportunity here in first-line melanoma, Ralph, how do you think that this combination would fit in? I think it's a very competitive space, of course, as we all know. That being said, I do think this is a different mechanism of action that has not, which is something that we've not seen in a while in cutaneous melanoma. Checkpoint inhibitors have been established for a long time. I do think if the data is positive, of course, that it could have a significant space to play in HLA-A2.1 positive patients. David, remind us of the timing, and also, are we going to see anything when you make this dose decision? The dose decision will be in, it'll be in the fourth quarter at this point. No, scientifically, I don't believe that you can really deconvolute two active agents in a first-line. You know, we've been misled many times, IDO, pegylated IL-2. We didn't plan it in the beginning to have a release of the data from the dropped arm. The question has come up. We've looked into precedents, and we can't find a precedent for that type of data sharing. We have to keep in mind the integrity of the trial and making sure that there's no unblinding. We haven't planned for it. What will be released, the IDMC will release which dose is selected, and we will release that information. Is there anything we can read into that? We can read into it that the IDMC is happy that the trial continues. I think, in phase 1, we saw similar activity and similar safety between the two doses, but it was not randomized. We agreed with FDA and Project Optimus to do it within this trial. I don't expect there to be a big difference, and we only have 30 patients per arm, so it's powered to see big differences. In the end, what we've decided is, and agreed with the IDMC, who is a group of experts, that they'll make the decision based on their expertise, and I trust them. Which is, what if the two doses look the same? You know, there's always going to be numerical differences. There's going to be safety differences. There's differences in terms of drug preparation that might come into play. There's differences in exposure that, you know, there's some theoretical differences that might make a difference. are your expectations on timing for that? How is recruitment going, and what are you thinking when we'll be able to see? The dose selection? Beyond the dose selection for the primary endpoint. Yeah, randomization has actually been going fairly well, and we are getting, we have hundreds, over 150 sites open globally. We have 150 investigators who want to participate in this trial. I think that tells you something there. Right now, we're penciling in a three-year trial. It started at the end of 2024, so the end of 2027. I think once we get into steady state randomization, we'll be able to better predict when we'll be able to complete. There aren't a lot of other phase 3 trials in first-line right now. One more question on that. The types of patients that you're seeing coming into your study versus other trials, anything that could impact the timing there? I don't think so. I don't think that there's anything really different. Let's move on to some pipeline programs. You mentioned PIWIL1 earlier. CRC does have a very high unmet need. What kind of data are we going to see here? How many patients? How many active dose levels? What should we expect? Yeah, so with PIWIL1, it's in late line CRC, which is a very tough tumor. T-cell engages in immunotherapy have not really worked in CRC, so it's a high bar. We designed the trial to move rapidly into earlier lines and combinations based on our experience. We plan to start that this year. Next year, we should have the data in-house for what does it look like as a monotherapy and dose escalation, and can you combine in earlier lines, and do you start to see something interesting in earlier lines? You don't expect to see anything interesting in later lines? It is still early. I mean, we're still in dose escalation. Certainly anything's possible, but CRC is a tough tumor. Remind us of the expression of PIWIL1. Depending on the location of the tumor, it can be up to about 70%- 80% positive, and about 1/4 of colorectal have diffuse PIWIL1 positivity. Remind us, are you doing intra-patient dose escalation? Will all patients we see be at active doses? Yes, we do that so that we can rapidly get to active doses as fast as possible. It started about a year ago, is that right? It started in December, so about nine, nine, ten months ago. We are going to see data now in November at AASLD for HPV. What does good look like there? Is this a program that Immunocore would take forward alone? Yeah, I imagine I bucket the HIV and HPV program together. I think that they're complementary in terms of providing information. With HIV, we showed that we can do something. It's not yet at the target product profile, but it's doing something. With HPV, it's a single dose. We want to just set expectations there. What good looks like for us is can we see some dose-dependent evidence of surface antigen changes, declines? Can we see dose-dependent increases in ALT, which is called productive transaminitis, because you're killing HPV-infected hepatocytes? Can we do that without causing massive liver decompensation? That's, to me, what would be success. I believe the HPV and HIV together are complementary in providing reason to believe. I guess one final one for you, Ralph. Will you be maintaining operations near break-even prior to any label expansions or drug launches? Our CFO would love this question. I think the goal is always, obviously, to become profitable. I think the main goal today is to advance the pipeline because we have, we're the pioneers in TCR therapies. We will continue to grow the cells. We will continue to invest, and we'll do so very diligently so that, you know, eventually we can get there. Great. Thank you both very much. We are very excited for 2026 for Immunocore. Thank you for hosting.