Good afternoon, everyone, and thank you for joining me at the Needham Conference, Healthcare Conference. First day. It is my pleasure to have with me Immunocore's management team, David Berman, Chief Financial Officer, and Mohammed Dar, the Chief Medical Officer. Maybe a good place to start, David and Mohammed, just a quick description of Immunocore's technological platform and how you're different from, let's say, some other T-cell engagers in the space. Yeah, Gil. Well, first of all, Gil, thank you for having us. We appreciate being here. Yeah. I'll start, Mohammed, and then obviously, feel free to chime in. Immunocore was founded on a T-cell receptor platform, and I think what's unique about our platform is we have the ability to produce high-affinity, off-the-shelf soluble TCRs that engage with intracellular cancer antigens. The reason that's important is for a couple of reasons. One, we believe it enables treatment of immune-cold tumors with a low mutational burden. That's one aspect. The other aspect is because it relies on HLA to present those targets from an intracellular perspective. It gives us access to greater than 90% of the proteome. That's a key differentiator versus standard antibodies, or typical bispecific antibodies, that rely on extracellular or membrane-bound targets that cover only about 10% of the proteome. We have a much broader access to the target population. The other thing that's unique is the modularity of the platform, what I was referring to on turning immune-cold tumors hot, if you will. We can also use it to engage T-cells to bring them in to fight infectious diseases. We can also flip the axis and down-modulate the immune system in a tissue-specific manner and to fight autoimmune diseases. Those are the three therapeutic areas that we're looking to address with the platform. Finally, I'll say, we have some validation on the platform, right? We were the first company to develop and get approved the first TCR therapy in KIMMTRAK, which has now been approved for uveal melanoma with a strong overall survival benefit, which obviously is the gold standard in oncology, which I think we're going to probably talk a bit more about. Great. Maybe just starting with KIMMTRAK, shown consistent growth over the past several years, actually. What do you attribute to the successful launch thus far, and how do you generate further growth from where you are now? Yeah. As you're alluding to, we're really pleased with the commercial execution of KIMMTRAK. We sold just over $400 million last year. We're now entering our fifth year on the market, and we're standard of care, right, across all major markets. Really, I attribute that success to two things, the people and the product. From the people perspective, we have an experienced team that had a lot of launch experience, and so we've had good execution from our commercial team. The other aspect is the product, KIMMTRAK's profile. Having demonstrated a very strong overall survival benefit, the hazard ratio of 0.51, has a very predictable and manageable safety profile in a patient population that had a very high unmet need. I don't think a product had been approved in uveal melanoma for 40 years prior to KIMMTRAK being approved. To answer your second question, if you look at growth, two different components, a growth component in the U.S. and a growth component OUS. The growth component in the U.S. has really come from two aspects. One is an increase in duration of therapy that we've seen over time, and then the second has been continued penetration into the community centers. That's really been a testament of that safety, that overall survival benefit and predictable safety profile that I mentioned to you earlier, that we've been successful there. OUS, while those same things that I mentioned hold true OUS as well, it's also been about expanding global patient access, right? We were approved in 39 countries. We have launched in 30 now. Really the growth OUS comes from those additional launches and maximizing global access for patients. The average duration of therapy has been increasing. How much more room do you think there is to grow there as it relates to the duration of therapy? Yeah. You're exactly right. It's been very interesting to see the duration of therapy. Why I say interesting is it's quite remarkable that we've now seen duration of therapy in the real-world commercial setting exceed what we saw in the clinical setting. We're now at about 14 months of duration of therapy versus the clinic was closer to around 10 months. As you sure appreciate, I don't know that's ever happened before. I'm sure it has, but it's incredibly rare to have an increased duration of therapy in the commercial setting than it is versus the clinical setting. While that duration of therapy is more mature now in the commercial setting, we still see an increase in those. I referenced that we're continuing to maximize global patient access and with additional launches. As we do those launches, we see that same pattern of duration of treatment increase in those newer countries. Great. I do want to spend a minute on some information that came public this morning. This is from a competitor called IDEAYA, and this is for darovasertib. Very good data in HLA-A2 negative, the other side of the uveal melanoma market that you guys are not in, but pretty impressive median PFS numbers and also response numbers. Now, obviously, an A2 negative is not a concern for you in the near term, but just looking into the future, this is a TKI, so theoretically can be used across the entire population. How would this slot into therapy, and do you think you're going to continue to see what is the sense of continued treatment of KIMMTRAK post-progression? Hi, Gil. I'm happy to take that on. I think there's a couple of things to keep in mind, even before we get to the data that was released today, which is this whole concept of treatment beyond progression, how we got here. The history is that during our phase I development, it was the investigators who were coming to us and saying, "Hey, look, I know the patients are progressing, and so per protocol they should come off, but there's clearly something going on here in terms of clinical benefit and that we want to continue the patients on the therapy." That was the original observation. It came from the clinic, from the investigators. Based on that feedback, we incorporated this concept of treatment beyond progression into the pivotal trial. As you know, not only was the trial positive, but among the patients whose best response is progressive disease, even that subgroup had better survival compared to the controls, comparing progressors to progressors. Ultimately, the third sort of data point comes from real world. Now that KIMMTRAK's been on the market for 5+ years, we're seeing that the treatment beyond progression is even longer in the real world. My experience is healthcare practitioners, physicians do not usually discontinue treatment if patients are benefiting, especially if the overall safety profile is favorable. That's true with KIMMTRAK because we don't see cumulative toxicity the way you might see with chemo, targeted therapies, and even with general IO checkpoint classes, where over time you can get more irAE-related activity. For KIMMTRAK, where we have an established survival benefit and it's an established standard of care in the 02:01 positive, we don't expect that this sort of observation is likely to change based on what the underlying rationale has been for physicians to do treatment beyond progression. What about slotting? Let's say both products are now on the market. How do you think this plays out? I'll start, and if Travis wants to add. As you said in your starting comments, Gil, the trial, the randomized trial, is being conducted in 02:01 negative patients, which is the sort of mirror image of the population that KIMMTRAK's approved in. So this is good for patients because there's nothing specifically approved in 02:01 negative. So provided the data, because we haven't seen the data yet, provided the data is presented publicly and is reviewed by health authorities, this would be a really good outcome for patients to have a treatment option. But I think the things to look at would be what is the survival, because we haven't seen the survival data. What is the toxicity profile? Because, as you know, targeted therapies, if you're taking them daily orally, means you also likely have chronic toxicities that are not insignificant and can lead to treatment interruptions or dose holds. Last but not least is, I think you need to see durability because they mentioned responses including CRs. You would want to see what's the duration of response in that group. I think we need to wait to see how the data stacks up, but it's all in 02:01 negative. KIMMTRAK's approved in positives. Now they have a single-arm study in a phase II trial in positives, but that's a single-arm trial. What KIMMTRAK has is randomized trial data with OS as the endpoint, so that always trumps single-arm data. I think that at least from a labeling and clinical practice perspective, generally slotting would occur following failure of a standard of care in the 02:01 positive group. That's where it would likely fit if they generate phase II data that appears to influence NCCN or other guideline bodies. Yeah. Gil, one thing I'll add on to what Mohammed mentioned is for us, it's continue to make sure we support KIMMTRAK and support with data. Two things, a couple of things. One, we had some real-world French data from a French registry last year presented at ESMO, that showed a 28-month overall survival, again, showing that additional benefit that we've actually seen in the real world versus where we've seen in some of the clinical study setting. Another aspect is we have the five-year OS data coming very shortly, next month at AACR. We're continuing. That's going to be an oral presentation, so we're looking forward to that data being presented as well. Later this year, we'll look to follow that up with some OUS real-world evidence data also. Great. That would be very helpful, actually, the five-year OS data. Well, we'll make a list of questions here as well. Does this preclude you guys going after other HLA types just because of how the therapeutic landscape's evolving? Yeah, I can take that, Gil. As you pointed out before, KIMMTRAK is specific to the 02:01 positive population based on its mechanism of action. If you think about the target population, the vast majority, 90%-95% of uveal melanoma cases occur in Caucasians. The largest HLA allele in Caucasians is the 02:01 positive allele. There are about 5%-10% of uveal melanoma cases occur in other ethnic groups. For KIMMTRAK, we haven't thought about other HLAs just because of that epi data. Where we have considered other HLA types is in other more prevalent, where HLA types are more prevalent, based on targets, like for example, in PRAME or other diseases, for example, in infectious disease for HBV, we've considered more other HLA subtypes that would be more relevant to the target population. Right. I do want to spend some time on one of your major readouts this year, TEBE-AM. Maybe just starting, just to frame that study, it's been going on for a while. What's the setting? Where are you aiming to slot in in the therapeutic landscape there? Yeah, happy to do that. The TEBE-AM target population is basically, it's a group of patients who have failed all available therapies, all available and approved therapies. This is the post PD-1 setting. In addition, they should have been exposed to CTLA-4. If they're BRAF mutant, it's after they've been exposed to BRAF-targeted therapy. It's a group of patients who have exhausted all treatment options. The other is that in this setting, there's no treatment that has shown a survival benefit in a randomized trial. That's the endpoint for TEBE-AM. If that trial is positive, this would be a first. This is even in the setting where, for example, TIL have recently received approval that's been based on response rate in single-arm trials. If you look at the median survival and landmark survival, it's no different from historical controls. In terms of how it might slot, I think if this trial is positive, as I mentioned, it's the first one that would have survival endpoint as being positive. It's off the shelf compared to TIL. It's a standard infusion. Yeah, it's a drug that's familiar. About half the patients with cutaneous melanoma have been treated by a physician who already has KIMMTRAK experience. It's something that physicians are familiar with that typically treat cutaneous. If I'm reading between the lines here, you're not expecting to really split the market. Would like for you sell maybe more of a, in tandem, and they might come even after, basically. Yeah, I think the reality is that TIL therapy is really typically used in a very specific subset. It's a group of patients who can have their tumor resected, can wait for the product to be produced, who can undergo conditioning regimen. It is a subset of patients, whereas, if KIMMTRAK TEBE-AM is positive, it's a pretty broad population that would be potentially eligible. As it relates to your investment, assuming everything goes well here, how much more do you need to invest in order to expand your commercial footprint, or is there a lot of overlap like you mentioned? Yeah, there's a lot of overlap, Gil. CFOs love synergy, so I like this one a lot because we do have a lot of synergy, obviously, with the current commercial footprint that we have. The investment to commercialize cutaneous is incremental. Mohammed actually referenced, we have 50% of cutaneous patients being treated by physicians that are familiar with KIMMTRAK. That gives us not only a lot of synergy from an economic perspective, but also provides a great foundation for us to launch the product when you have a lot of familiarity with the product already from uveal melanoma. I do want to spend a second on pricing. I've asked this question literally every year. What do you think? I don't see WAC pricing changed, but is there other levers you can pull here as it relates to a larger population of cutaneous melanoma? Yeah. As a general pricing philosophy, we're going to price our products based on unmet need and the value to patients first and foremost. A lot of that is informed by the data. To sort of address both of those things, as Mohammed just alluded to, this patient population has a very high unmet need. There's really no standard of care because they've progressed. There's no therapy that has shown an overall survival endpoint. Our trial is designed with a primary endpoint of overall survival. If we're able to demonstrate that, we feel very strongly about the pricing opportunity here. Not to forget the ADaM study. Any setting of expectations around this adjuvant setting study? Yeah, Gil, happy to take that. I think, a couple of things. One, ADaM currently is the only active adjuvant uveal melanoma registrational phase III trial. Just as a reminder, it's focused on patients who are at high risk of disease progression, and the primary endpoint is recurrence-free survival. The expectations for ADaM were really set based on observations we made from our phase III frontline metastatic trial, where while the overall trial was of course positive in all patients across the different subsets benefited from KIMMTRAK relative to the control group, what was interesting to see were the patients who had smaller tumor lesions, less than 3 centimeters, had the largest PFS benefit. As a reminder, the overall hazard ratio was 0.73, but in the group that had less than 3, it was 0.68. This further supported the idea of moving KIMMTRAK to an earlier setting, i.e., adjuvant. In terms of timing, right now, it's still early days. The trial's been open, and it's being conducted by the EORTC, so it's a cooperative group study. Based on sort of the current outlook, the intent is to complete enrollment by 2028. Switching gears to brene, let's not forget the PRAME franchise here. Going frontline against Opdualag in metastatic CM, can you help us understand the choice of the control and maybe a bit of the timelines for the study? How much improvement over Opdualag are you hoping to see, I mean, not just from a statistical perspective? Yeah, sure. Happy to take that on. Just to step back in terms of the trial design and the rationale for including Opdualag, our goal at all times when we're designing these pivotal trials is not only to have a statistically significant outcome, but also one that's clinically meaningful and, of course, commercially relevant. At the time we were designing the study based on feedback from global KOLs, there was certainly feedback and insight that people were beginning to use more PD-1 combinations. As a way to anticipate where the field was moving, the design incorporated this sort of composite hybrid control, which includes nivolumab or Opdualag, not at the investigator discretion, but based on global approval or based on the country-level approval in the all-comers population. That's sort of the history behind the inclusion of Opdualag is anticipating where we're moving to and reflecting sort of real-world practice and the trial design where we wanted to go into all-comers. In terms of the sort of timelines, right now enrollment's progressing well. Last year, we completed the Project Optimus dose selection portion of the study, and currently we're aiming to complete enrollment by the end of 2027 or early 2028. In terms of the level of benefit that we're looking for, while we typically don't get into the specifics of our statistical plan, again, as I mentioned before, we are looking for generally a clinically significant and commercially relevant improvement. In general, in pivotal trials, that's at least a 25% improvement relative to control. Now, assuming everything works out and you're super successful in both assets, how do you view the interplay between brene and tebe? I mean, we've seen data for relatively low activity for brene post-tebe. Well, now we might have tebe post-brene. Any thoughts there? Yeah, thanks for the question. I think if we are able to get a successful TEBE-AM study based on sort of the benchmarks or thresholds that I was alluding to, then I think we're pretty confident about our ability to compete commercially in this frontline population, which is roughly around 10,000 patients. This is the PRISM-MEL-301 study. In terms of the observation that you're referring to, we have seen clinical benefit for patients who have received tebe, like for example, in uveal, and then came onto brene. It's not that we don't see any benefit. We definitely see benefit, and there are people who have very prolonged survival. We've had some patients who started on brene and then moved on to tebe as well. Similarly, there are examples of patients that had long survival. What we don't yet have is sort of systematically studying sequential treatment in a randomized trial in cutaneous melanoma, which is the scenario that you're talking about. So I think the other thing to keep in mind is the fact that these segments are different, right? So the PRISM-MEL-301 population is obviously a frontline, and then the TEBE-M is going to be a later-line population. So we are targeting two different populations, and currently the data that we have is anecdotal, but suggests that there is still some evidence of activity, but we haven't studied it systematically. I do want to spend also a minute on ovarian cancer. You've shown some data on platinum-refractory patients. What is the logic of you looking at the platinum-sensitive populations? Yeah. No, that's a really good question. We know now from a lot of our clinical data and also sort of mining our translational data that this mechanism of T-cell engagers works best in earlier lines where the T-cell health or T-cell fitness is highest, and that sort of supports the underlying mechanism. That's one point. The other point is that a key characteristic of the platform is good disease control that leads to long-term survival benefit with a safety profile where you see most of the adverse events in the first couple of weeks, and then with the longer the patients are on treatment, the safety profile actually improves. All of those features lend themselves to an earlier line setting, especially a maintenance setting in ovarian, which is where we're working on generating data with brene, where patients have usually been debulked, and the goal is to have prolonged disease control that ultimately translates into survival. You want a safety profile that will be acceptable to patients who are on the maintenance setting. This is all built on the fact that we saw monotherapy data with brene in a late-line platinum-resistant setting. We have monotherapy data, and then mechanistically, it makes sense to go to earlier lines because of the T-cell fitness observation. Basically improving outcomes by doing better mop up post-resection? Yeah, exactly. You guys also have some lung efforts. Is there any update on this? I think we ask this every time. You're saying, Gil, about lung? Yeah. Yeah. I think, compared to ovarian, where we already have seen a signal and we're building on that by moving to earlier lines, I would say for lung, we are still in signal seeking. Lung is certainly more heterogeneous. Here our efforts have been really focused on signal detection. As you know, lung has a bunch of different molecular-defined subsets. That's where we've targeted enrollment for monotherapy. In addition, we have looked at combinations with standards of care, so we can move to earlier lines, including combination with osimertinib and EGFR mutant lung. That's the cohorts of data that we're focused on generating the follow-up on that we hope to share in the back end of this year. Okay. We also saw some data from competitors, specifically for your half-life extended types. You guys have your own. What kind of gates your decision-making around which one to move forward with? Yeah, it's a good question. I think we're in a unique position where obviously we have several years and several hundred patients' worth of data with brene in the clinic. Essentially our PRAME-HLE is brene with an Fc attached for longer half-life. We're conducting exactly that experiment, which is to test whether a longer half-life and the ability to perhaps get higher exposure leads to perhaps better outcomes and, at minimum, our base case is improved patient convenience and less frequent dosing. With that said, the power of the platform is clearly demonstrated with KIMMTRAK, where even though we don't have a long half-life and we still have a very significant and clinically relevant OS hazard ratio. We know even with a short half-life, you can deliver very meaningful clinical benefit. Really now the question is can you improve even further on that with the longer half-life? We've set up the experiment to answer that question in the clinic. Are there any challenges to enrollment in PRAME just because of participation from others in this space? Is this big enough patient pool? It's not an issue. Yeah, no, I think from a phase I/II perspective, we usually focus on a mix of investigators, some that are typical phase I investigators, but others who have a focus on a particular tumor type that we believe is good to enroll from a PRAME perspective, let's say ovarian or melanoma. With that kind of mix, we haven't had any challenges to try to enroll into our phase I/II trials. Again, switching gears, I'm going to talk a little bit about the infectious disease franchise. You've guided for additional phase I data in HIV to be presented in the second half. What should we be expecting? What do you think you're ultimately hoping to accomplish with this program? You've talked about functional cures in the past. We just want to understand the context as it relates to competition. Yeah. No. Thanks for the question. I think the reality is the goal for the program, as you alluded to, is something called functional cure. It's a very lofty goal. Obviously, to date, no one in the field has achieved this goal. Ultimately, from a drug development perspective, it's going to be an incremental stepwise approach as a field and certainly for us with this trial. As we shared last year, we're in the middle of a dose escalation in the MAD portion of the study, and we saw some very interesting signals where there was an impact on the viral reservoir, and there was a delay in the viral rebound after you stop all therapy with really acceptable safety, no dose-limiting toxicity. What our goal for this year is to continue escalating to higher doses, higher exposure, and ask the question, with higher exposure, do we see even better effects on the viral reservoir as well as the viral control after you stop therapy? Since this is a phase I trial, the cohort sizes are small, but we do have the ability, if we see something, we can expand and add additional patients to follow up on any promising signals. There was a little bit of CRS in some patients. Is this any reason for concern as it relates to physicians who treat patients with HIV? That's a really good question because obviously, oncology and patients' willingness and benefit-risk equation is quite different from HIV, or people living with HIV. The cases that we have seen to date have all been generally grade one and resolve very, very quickly, which grade one means just fever. They resolve usually pretty quickly, within a few hours. With regards to grade two CRS, if we were to see that, which is quite possible as you push the doses higher, it would really depend on a couple of factors. One is how quickly does that reverse, and what is the associated benefit? Is the benefit worth the risk? Of course, we've learned from oncology that you can mitigate this by giving pre-medications like steroids. That's certainly built into the study design as well. Are there other infectious diseases you think your platform is particularly suited for? The way we're thinking about it, Gil, is that since the platform and the mechanism is a T-cell engaging mechanism, it's really infectious diseases that result in chronic sort of infection of the host where the infection is able to avoid the patient's own immune system that are sort of the ideal target. In theory, our approach could really be applied to any sort of intracellular pathogen, bugs that basically hide inside cells and try to escape the host immune system, particularly those where there's no good treatments like antimicrobials or antiviral or there not even any available therapy. That's sort of how we're thinking about it. Right now we're being data-driven and focusing our efforts on HIV. Maybe rid the world of herpes simplex. Always comes back. All right. Other programs specifically for autoimmunity, can you provide a bit of background on some of these? Your ability to accurately target specific tissues is of particular interest here. It's a bit of an unusual feature. Yeah. This is something we're particularly excited about because in part, David Berman opened with sort of what the core strengths of the company are, which is this platform that allows modularity. It's not only the modularity of the platform, it's also coupled with some core strengths of the company that sort of highlight how we are approaching the autoimmune space. One, obviously as you know, Gil, we've been focused for 10-15 years on oncology. During that time, during target discovery, part of the process is to try to identify tumor-specific peptides that we can target with our TCRs. As part of the validation, you look for peptides in normal tissue to make sure that they're not going to cross-react. Naturally, we had a library of normal tissue peptides for HLA-A2, which we could leverage and say, "These are only expressed in skin. These are only expressed in gut. That was one of the core strengths of the company was this deep expertise in immunology and proteomics. The other was that good deep understanding of disease biology. For autoimmune, really the goal was to come up with something that's really differentiated from the rest of the field. You were kind of alluding to this idea of tissue tethering or tissue-specific immune modulation became the concept that the company became focused on, and to see how we could use our TCR bispecific to achieve that. The last sort of component of the company core strength has been this world-class protein engineering. Once we came up with the concept of tissue tethering, they came out with a bispecific that can target specific tissues. As you know, our type 1 diabetes program has submitted a CTA, and we're aiming to get the first patient dosed in the next couple of weeks or a month or so. The other one is potentially for atopic dermatitis targeting CD1a. The protein engineers have developed these bispecifics that can target either the pancreas or the skin in a very specific manner, and then get the PD-1, which is the effector side of the molecule, into not only that tissue, but into the actual immune synapse, which we think is a really important concept. It's tissue tethering, and then to get the immune modulation into the T cell synapse in a very specific manner. We're really excited by the prospects of our autoimmune programs, which really represent a novel approach compared to what's currently in the field. Maybe a bit of a forward-looking question. As it relates to your infectious disease and autoimmune portfolios, is this something you would be more inclined to partner or is this truly indication by indication specific? I can take that. Yeah. The short answer is yes. We're open to partnering as long as it's at the right time and it makes strategic sense for us to do it. If you think about where we're at with our current infectious disease and autoimmune programs and that we're well capitalized, we have the ability and optionality to take these programs to significant value inflection points with relatively low amounts of capital. As we think about starting the type 1 diabetes program, hopefully we'll be dosing that patient here by the end of the quarter, and then getting our CD1a program and the CTA filed later this year. It takes a relatively small amount of capital to get to that big inflection point, and then we can begin to think about how we may potentially share risk and help maximize the value of programs with parties that are more well established in those two areas. I'm asking the reverse of that question. Just given your cash flow, have you given consideration to business development? Yeah, certainly so. That's a continuous process for us. We're always looking and assessing, to clarify, inbound business development opportunities that we may deploy capital for. Obviously, those need to be the right opportunities. We're going to be disciplined in those business development efforts that build on the scientific and core expertise that we have and leverage the footprint that we have. In fact, this is the reverse question, to your point of what I just said on the out-partnering. We have an established development and commercial capability built in oncology. I think it's fair to say majority of our inbound efforts are focused there in looking for ways to build upon that scientific expertise and that footprint. Maybe that's a good place to kind of round it up with financial position. Where does it get you? Yeah, very well capitalized. We have just over $860 million of cash on the balance sheet at the end of the 2025. That alongside continued commercial execution with KIMMTRAK and revenue generation with KIMMTRAK, combined with the fact that we're going to be disciplined with both our SG&A expenses and also be data-driven with those R&D investments, that really allows us to fund the portfolio for the foreseeable future. Great. That was most of what I had. Maybe this is your opportunity to highlight something that I may have not touched upon or any kind of last messages to investors that you want to leave. I think you hit the majority of it. What I'll say is maybe a summary of we have very strong revenue generation from KIMMTRAK that is effectively funding the company, and now we're seeing those investments come to fruition, with TEBE-AM coming, hopefully the data as early as the end of this year, continuing to execute the other two phase IIIs that we have ongoing beyond TEBE-AM. We have a lot of early-stage clinical data coming this year across PRAME, HIV, and then initiating our efforts in the clinic in autoimmune. Very exciting year for us this year. All right. I'd like to thank you both for your time today. Yeah. Thank you. Thank you so much. Take care, Gil.