Immunocore Holdings plc - ADR Stock

Good afternoon, everyone. I'm Sean Laaman, Head of U.S. Mid-Cap Biotech Equity Research here at Morgan Stanley, and welcome to Morgan Stanley's Global Healthcare Conference.

Before we commence, just to make you aware of some important disclosures, please see those disclosures at the Morgan Stanley [ Research Disclosure ] website at www.morganstanley.com/researchdisclosures. And if you have any questions on those, please reach out to your Morgan Stanley sales representative.

For this session, we have Immunocore, and from Immunocore, we have the CEO, Bahija Jallal; and CFO and Head of Corporate Development, Travis Coy. Welcome both of you, and thanks for your time.

Thank you for having us.

Maybe the first couple of questions just on the macro outlook. So how is the rise of China origin innovation changing your competitive positioning, if at all, and does it change your R&D and BD playbook?

Sure. First of all, thank you for having us. China has been fastest in areas where the biology is known, for instance, like checkpoint inhibitors, ADCs, and bispecifics against extracellular domain. So the pressure is real, and I think if your edge was to get to the -- a known target fast, that edge is very thinning. Where we sit, we are in the TCR, and speed is not our -- it's not the edge that we go after because we are really dealing with something very complex inside the intracellular, and that complex of HLA and peptide, how it interacts with the TCR, that means TCR engineering and specificity is very important.

So that's not, the speed is not our problem right now, but really finding the right target is. I think where it has an impact now is definitely on the business development side of things, and I think when you look at that, China definitely set the bar for what a Phase I asset, for instance, is. And with that supply and demand, really when the cost is not an issue, then -- and because of that supply and demand, that -- the bar becomes very higher, and the scrutiny of -- and the judgment of what assets you bring is very important. And I would say, I will finish just with this one. It's not -- the differentiation is no longer how fast you can get there, but how you can have something that cannot be -- that's harder to copy, basically.

Sure, thank you. And you -- are you implementing AI adoption across your business? And has it already changed the decision, a timeline, a cost, or a POS?

Yes, I think it's an amazing technology. I would describe it that way. What it had already had an impact for us is the upstream. So basically what we used to do is, like I said, the complex of HLA and peptide is really, really very finicky, and how the TCR sits on that is something that we used to do crystal structure to even know how this is happening. And you can imagine that it's tedious, it takes time and stuff like that. We don't do it anymore. Thanks to AI simulation, and things like that. We actually do all that aspect in silico.

I think where I am really excited about, I cannot say that we do it systematically today, is when you look at the whole drug development process. And if you can just focus on compressing time, and you improve by 1%, this is what I'm -- the challenge I'm giving my organization. You can improve 1% in every single step. You can imagine how we can reduce that lengthy time. So things like what we do today, for instance, how to answer the RFIs, [ which ] come from regulatory agencies, how we automate all that, and how we can put AI into work. So there is a lot, lot to do, and I'm really excited about that.

Wonderful, thank you. And last question before we go Immunocore specific. Which policy variable, FDA, Medicare negotiation, MFN, tariffs, or global pricing, matters most to your economics, and what have you changed, if anything, because of it?

Yes, yes, so I think I would, without hesitation, I would say FDA and predictability. I think that has a huge impact. I think where we sit as a company today, we are with KIMMTRAK, more of a rare disease, so our -- with small populations. So the impact on tariffs and pricing and stuff like that doesn't fall on us the same way as most of the big companies here. Having said that, where it's really we cannot hedge is with the FDA, the predictability, because we have -- for instance, we have 3 Phase III trials that are ongoing. That's millions of dollars. That's also a long time. And what you want to have is that the goalposts don't change by the time you arrive there. So I would say that, that's really the big thing. We didn't change anything, and I don't think anyone can tell you that you can change things, especially when it regards to policies that will change anyway. But you have to be prepared. You have to run scenarios for yourself, and that's exactly what we're doing.

Thank you. I've got a question here on the platform and then I'll go specific. I might put my TEBE-AM questions closer to the front now, but -- after this morning. But on the oncology side, what still differentiates an ImmTAC bispecific from the growing field of TCR-based and other T-cell engager approaches, 5 years post the commercialization of the first one?

Yes. It's -- I'd like to say 5 years into it, which I really love. From being a pioneer in this area, I would say, it is no longer a differentiator that the TCR-based therapies are a category of compounds or how to treat patients, which is great. What it still is, I think, is basically we have the possibility to access 90% of the proteome, the intracellular target, we can treat more cold tumors and hot tumors at the same time. And what is true 5 years into it is we took a molecule from the beginning to becoming a standard of care in a disease that didn't see innovation. So that's really, for me, the 5 years. But I want to finish just with 1 point that's really important, and how we differentiate ourselves is the fact that we treated more than 2,000 patients. And we have data not only in the clinic, but in the real world. And what's really important is how we take this information back to research to continue to innovate in that space, and that's differentiating, and that's -- we can basically say that we have that unique to us today.

Wonderful. Thank you. TEBE-AM is a meaningful near-term catalyst, top line OS possible by year-end, and enrollment down to the teens. In your view, what would a positive result mean for how the audience should value the earlier line expansion story?

Yes, I think -- so we're very happy with the announcing that we finished the trial. That will be for a company like us, the second Phase III trial that we did with this team, so I'm very happy with that. And I think the answer to your question is two parts, right? So 1 is the commercial one, which today, we treat 1,000 patients in uveal melanoma, if we are in the lucky situation where this is positive, it expands to 4 -- an additional 4,000 patients. And I think that is really that expansion on the commercial level that we look forward to. And the -- on other story for Immunocore, for some reason, I think people think that uveal melanoma was a lower bar. Actually, it was a really high bar because it was no innovation in 40 years or something like that. So that, for me, that was the highest bar for KIMMTRAK, but here it will expand then into cutaneous melanoma, we already showed ovarian. So I have no doubt that this platform will expand even more.

Sure. Thank you. On the bar for success, the 1-year OS benchmark in second line has been around 55%. Your Phase Ib showed roughly 75%, and you've designed the study for a result that's both stat sig and clinically meaningful. What magnitude of OS benefit do you think the community would view as genuinely practice-changing?

Yes. It's -- I've been saying that today that I am not a few months before the data put any numbers out there, right? So I'm not going to do that. Having said that, I think what's practice changing in this population is definitely bringing, it depends on where you stand, right? And in this population, on second line-plus cutaneous melanoma that have basically nothing, bringing an overall survival will be practice changing because that's basically a very solid and golden standard in oncology. So if we're lucky enough to have that as positive, I think that's practice changing, and that's what we look forward to.

Sure, and I'll ask this question, but I think you'll [ pat ] me back, but just to the 3 arms, which do you think has the most importance for any commercial label?

I think we can deal with the commercial any way we have that. So we have in the trial, we have -- we're really in a good position where we have pembro plus KIMMTRAK and KIMMTRAK by itself. If KIMMTRAK by itself is the best way, we know how to deal with that, and it will be easy. If it's pembro plus KIMMTRAK, if that's the best for the patients, we'll adapt.

Sure. Moving on slightly, on ATOM in the adjuvant setting. You've detailed around 1,200 annual patients, and ATOM being the only active Phase 3 in adjuvant uveal melanoma. How do you think about the broader opportunity here, and can you share any detail on the enrollment progress?

Yes, definitely. So I think the adjuvant trial is really a must for us to do because these patients have nothing. So once they -- in uveal melanoma, 50% of the patients, after they remove the primary tumor, they basically are at high risk, what we call a high risk of developing metastasis into the liver. But they don't really know, they have nothing to prevent that, so they go through basically, I call it wait and worry. That means control every 3 months, basically, if the metastasis is happening or not. So we know from our trial that, especially the KIMMTRAK trial in Phase III, that when the tumor is very small, like the hazard ratio was 0.56 in our trial, but when we look at -- and when we look at the small tumors around less than 3 centimeters, the hazard ratio drops to 0.36. So that's really what encouraged us to go into adjuvant where you're dealing with most probably seeding cells.

So the population there, the high-risk population, would be around 1,200 patients in addition. So we talked about the cutaneous, if it works, that 4,000. So we'll be looking at above 6,000 patients in addition if the two trials are positive. So it's recruiting well. It's recruiting, we're doing it with the EORTC, it's recruiting in Europe, and we opened sites also in the U.S.

Sure, thank you. Okay, just going back to KIMMTRAK in UM. So I think you're 70% or in excess of penetration. And how do you think about the underlying growth rate from here?

Go ahead.

No, happy to. Thanks, Sean. As you alluded to, it's something we've been really proud of now that we're in the fifth year in the launch is the penetration we've been able to achieve across all major markets is 70% or higher. That comes from being the established standard of care in those settings. And as to be expected with any mature product that's been on the market now, you do begin to see growth moderate. And we're starting to see some of that, and we'll expect that moving forward. That being said, we continue to expect growth.

A few areas that we're focused on. One in the U.S. is continuing to increase that penetration into the community setting. And then outside the U.S., it's about two aspects, it's one, continued increased market access with additional launches, but then also with the more relatively new markets that we've launched, we continue to see that duration of therapy increase beyond what we saw in the clinical setting. And that was a dynamic we saw in the U.S., and it's nice that we're seeing that OUS as well with those newer markets.

Sure. And what's driving that duration?

The -- it's a really remarkable drug because usually in the clinical trials, you get much higher duration of treatment than in the real world, right? The trials are more controlled and so on. Here we see absolutely the opposite, right? So the trial we are at 10 to 11 months, and here we are at 14-plus basically. And it came to two things, one is the fact that usually in a trial, the -- you stop at the radiographic progression, if you will.

The clinicians don't stop if the patient is doing very well in the real world, and that's exactly what's happening. There was -- this is a new mechanism that's not, with -- the patient -- the investigators are the ones who told us that patients, even with pseudoprogression, I would call them, do very well in -- with this drug and continue to do well. So they continue beyond progression. And the second thing that's really important is we brought the 5-year survival for this drug that also gives more evidence for the investigators.

Sure, thank you. Last question on KIMMTRAK. But -- as it relates to the competitive dynamics, we have some data coming up on ESMO from IDEAYA on darovasertib. How do you think about KIMMTRAK's first-line position in HLA-positive uveal melanoma being insulated versus potential of share threat over time?

Yes, so I think the -- to talk about the data that's coming or the data that was -- that were published actually or talked about in the conference, it's a good news for HLA-A2 negative patients. They're not eligible for KIMMTRAK, and that's a good news for them. Any other data, I can't really speculate until I see the data. We have not seen the data yet. It's coming in October, so we'll reserve that. What I can say, anything -- here is what any compound that needs to displace or wants to displace the standards of care, which is KIMMTRAK in first line needs to do.

One is basically you have to displace the standards of care. It is standards of care in every country where we went. In most of the countries where we went, it's standards of care. It's very well penetrated, but also the most important thing for me is the 5-year OS. This is the disease that's counted in months. They're not -- this is not something that takes years, it takes months once you're diagnosed with metastatic.

And what we've shown in 5 years, if you allow me, 2 things that are really important. One is if you were treated with KIMMTRAK, you double the chance to be alive at 5 years. But most importantly, 44% of the patients who are alive at 5 years had only KIMMTRAK. What that gives us is really arguing the actual sequencing, that to be alive at 5 years, you have to have had first KIMMTRAK, you can't leave it to later. And the second thing is that you have to continue taking KIMMTRAK. So those are backed with data, not with just what we say.

Thank you, thank you. That's a great discussion on KIMMTRAK. So moving on to brenetafusp and the PRAME franchise. So just sort of measure your confidence on PRISM-MEL-301 and what -- what's your confidence around it clearing the bar?

Yes, so I think there are 2 things that are important for PRISM-MEL. So this is basically looking at the first-line cutaneous melanoma in combination with nivolumab compared to nivolumab by itself or nivolumab-relatlimab. So the -- from the mechanism point of view, cutaneous melanoma has a high expression of GAAP100 PRAME, so I went into GP100 -- sorry, has a high expression of PRAME. And the other thing is that we have shown that PRAME is active as monotherapy, and that was very important for us. If we're going to go into any combination, we have to show that we have monotherapy activity.

So we show that we have monotherapy activity in first -- in cutaneous melanoma. In cutaneous melanoma we also showed that basically we have even higher than when we compared to nivolumab-relatlimab. And we have shown with our platform that if you move earlier in treatment, basically, if you move into first line, you have a much better T-cell fitness. So this, what the data that I talked about was a late line, so coming into first line, we believe that's going to work even better.

And then combining with nivolumab, these are 2 mechanisms, first 2 active agents that should be at least an additive aspect to the combination, and I believe will have also a synergistic effect because these are 2 complementary mechanisms or 2 different mechanisms that can add to each other. So we have -- the trial is going well, knock on wood. And we hope to finish by end of '27 the recruitment in that trial.

Wonderful. Thank you. On IMC-P115C, which is the half-life extended PRAME molecule, how do you think about less frequent dosing for adjuvant or earlier line patients?

Yes, I think, look, always, we went into the high half-life extension for -- to test the convenience, it's always important, the convenience for the patients, even if we did it differently in PRISM-MEL. So the nice thing is that the half-life extended molecule is exactly the same as the brenetafusp that's in the clinic, and what we're adding to it is just the Fc to increase the half-life extended. So we have the possibility to really compare and contrast and use the data from brenetafusp for the half-life extended.

Thank you. And I guess, what are you looking for in the early dose escalation data to decide whether that becomes a go-forward PRAME asset over brenetafusp in some settings?

Yes, so I think 2 things that I'll be looking forward to. One is, does the -- what we predicted for the PK, what we modeled for the PK preclinically. Does it really translate into the clinic? That's an easy thing to do in the first dose escalation of the product. And then the second one is because we are testing it in cutaneous and in ovarian where we know brenetafusp is active, we can directly compare. And I think that's exactly what we're doing right now.

Sure, thank you. And moving on to the autoimmune and infectious disease. The ImmTAAI, can you walk through why that this same platform that activates T-cells against cancer can be flipped to suppress them and why that should be more precise than systemic immunosuppression?

Yes, so I'm really excited about that. Like, maybe it showed. It's -- the fact is how the platform, and that's why I came to this organization, to Immunocore because really the excitement about the platform. If you think the platform has 2 components, right? The first component is that HLA, TCR complex and peptide that binds directly into -- specifically into an organ.

And then the second part is what brings basically what we need to do. Do we bring the T cells, do we activate the T cells to kill the tumor, or we use that to actually inhibit the T cells and switch off. So I'll just talk about the mechanism in HIV, for instance, is the same as in oncology. You want to kill the cells there. But in autoimmune, it's the opposite, which is exciting. So then you would ask me, what's the difference? We have systemic. Why -- as you asked, why we have the systemic? The systemic works, without a doubt.

When we think about steroids, they work very, very nicely. The problem is they work everywhere, even in organs where there are healthy organs, and that's why you see the side effects are happening in the muscle, in the joint in people having diabetes and so on.

Then the second innovation that was really good in systemic was the biologics, right? But there you are actually, you have a selectivity of the target, but that selectivity once you inhibit the target like the TNFs, it's also in healthy tissues. So TNFs, they're known, you get also infection. So what we're trying to do is a new paradigm. Can we go specifically to the organ that is affected and only treat that organ that's affected? And that's basically in type 1 diabetes is the beta cells. And that's really why I'm so excited about that.

Awesome, thank you. And on the diabetes program, strategically what's the readout you're watching? And how quickly could C-peptide give a real signal of whether you're preserving beta cell function?

Yes, that's a really great question because exactly why we went to type 1 diabetes, because it allows us first to test the whole hypothesis of the T cells. The second is because we can go into patients directly, not healthy volunteers. And third is we can get in single ascending dose and multiple ascending dose, that means smaller trials, we can find out if this molecule works or not.

So in the single ascending dose, we will answer one question, does the product, basically the compound binds to the beta cells and only to the beta cells, we can test that. And the second, in the multiple ascending dose, we can actually address the efficacy question right there, and that's because we will be actually following the C-peptide, and we know that the C-peptide has been now accepted by the FDA as a good surrogate for activity in an accelerated approval, like for anti-CD3, so we can with not a huge, huge amount of money or time and everything, find out if this works or not.

Wonderful, thank you. And still on autoimmune and thinking about your HIV program, thinking to a readout next year, 2027 -- in 2027 obviously, what would it need to show the industry that a functional cure is within reach?

Yes, it's really in steps. I think the bar there is much higher. We know that the bar for cure in HIV is much higher. We are dissecting, looking at the mechanism, looking at how things are working. So we have a multiple ascending dose, we presented some data showing that actually something is happening, that we can at least delay some of the rebound of the virus. We showed 2 weeks ago or something like that, the translational work and understanding the biology.

So we didn't believe that we reached the dose that we can. So we are continuing to dose escalate. We did actually escalate to [ 1,200 ]. Now it's looking at can we continue to see dose response and then understand more. So there it's really trying to understand that mechanism and how we can tackle it with this molecule.

Wonderful, thank you. And for Travis, as Head of Corporate Development, how important is BD for you today? Or are you primarily focused on internal R&D?

Thanks, Sean. Bahija referenced the need to continue innovation, right? And so for us, business development is part of that -- part of accomplishing that need to continue innovation. And so as we look for opportunities, and that's just as important as it is alongside internal R&D. So we look for opportunities to enhance the platform, look for opportunities that build upon our clinical capabilities and expertise.

We look for opportunities to expand market access. All of those things are sort of right there alongside internal R&D while making sure we're cognizant of the fact that we don't want to jeopardize the execution of internal R&D. We don't want to distract from that, while complementing it with those capabilities and expertise that we've built. So it's part of our DNA.

Sure. And I guess, can you walk us through your capital allocation framework? You're sitting on around $880 million, I think, with 3 Phase 3 trials running and when it comes to execution, how are you thinking about capital allocation and can you remind us of how you're thinking about the cash runway?

Yes, happy to do so. So 3 key buckets for us with respect to capital allocation. One is making sure we maximize KIMMTRAK. That includes both the current uveal indication that we have, as well as the potential for upcoming cutaneous melanoma indication. The second is making sure we continue to invest and execute on the 3 Phase III studies, right? And then the third is, ties back to actually what Bahija and I have both highlighted is, making sure we're not complacent around the platform and continuing to bring the platform forward, and that includes early stage R&D as well.

To your point, we are well capitalized with $880 million on our balance sheet as of the end of Q2. That really allows us with KIMMTRAK revenue being cognizant about our capital allocation and making sure we're disciplined with our SG&A, making sure we're data driven by the R&D investments that we make, that allows us to fund the portfolio really for the foreseeable future.

Thank you. And your platform now spans oncology, HIV, and autoimmune. How are you thinking about the balance between spend on the oncology side versus the infectious disease or autoimmune programs to focus capital? And how do you think about partnering as a corporate development lever versus doing it all in-house?

Yes. So as you break down, this is another way to break down the capital allocation question that you just asked. If you look at where we're spending today, our footprint is most established in oncology, right? It's where we have a development and commercial footprint.

So as we think about the HIV and infectious disease programs, and Bahija was alluding to this a little bit, we're likely to pursue a partner to maximize the value of those programs, but we want to do so at the right time and in the right way. And I think because of the capital -- relative capital efficiency that is needed in order to be able to take those programs to the next inflection point, that's when we'll begin to look for opportunities to partner those programs.

Wonderful. I have a final question, and that is, is there anything that I didn't ask that I should have, or is there a message you'd like to leave investors with, or both?

No, I think we did a tour of what we have. I think the -- again, very, very much excited about KIMMTRAK and what's doing with the patients. And I think these stories are really what brings us to work every day. But I think KIMMTRAK is not stopping there. I think we have a lot of possibilities with KIMMTRAK.

But the platform as a whole is not only in oncology, it's just the start, frankly and -- but also outside of oncology. We're extremely excited about that. But right now it's about execution. We have -- we finished the trial today. We still have 2 Phase IIIs to go. So I think that's about that. And what you're going to hear from us always is execution, execution, and focus until we bring the second phase of growth of the company.

Wonderful, might be time to call a close to things to give everyone a couple of minutes back, but thank you, thank you so much.

Thank you.

Thank you.

Greetings, and welcome to the Immunocore conference call and webcast. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Ryan Baker, Vice President, Investor Relations. Ryan, please go ahead.

Good morning, and good afternoon. Thank you for joining us on our Q2 and first half 2026 earnings call. During today's call, we will make some forward-looking statements, which are qualified by our safe harbor provision under the Private Securities Litigation Reform Act of 1995. Please note that actual results can vary materially from those indicated by these forward-looking statements, including those discussed in our filings with the SEC. On today's call, I am joined by Dr. Bahija Jallal, CEO of Immunocore, who will share achievements from the first half of 2026. Ralph Torbay, Chief Commercial Officer, will review our Q2 first half KIMMTRAK results and recently published 5-year overall survival data. Dr. Mohammed Dar, our Chief Medical Officer, will provide a pipeline update; and Travis Coy, our CFO and Head of Corporate Development, will provide some key highlights from our financial results reported earlier this morning. I will now turn the call over to Dr. Bahija Jallal.

Good morning, and good afternoon, and thank you for joining us today. Before I start, I would like to welcome Ryan Baker, who joined us last week as our new Vice President of Investor Relations. So welcome, Ryan. Guided by our mission, we have continued to execute as planned across the business. We remain focused on our 3 strategic priorities: maximizing the value of KIMMTRAK, advancing our melanoma portfolio and expanding into other tumor types and realizing opportunities in infection and autoimmune diseases. Starting with KIMMTRAK, we generated $223 million in net revenue in the first half of the year, representing 16% growth compared to the first half of 2025.

At AACR in April, we presented the 5-year overall survival data that showed that KIMMTRAK doubles the likelihood of being alive at 5 years for patients with HLA-A*02:01-positive metastatic uveal melanoma. For a disease once measured in months, 5 years is extraordinary. And some of those patients are alive today because of this medicine. This is why we come to work every day. In melanoma, we are advancing 3 ongoing Phase III trials: TEBE-AM, ATOM and PRISM-MEL-301, an important differentiator for a company of our size.

Beyond melanoma, we expect to present updated PRAME data in additional tumor types by the end of the year and to provide initial pivot data in 2027. In autoimmune diseases, the first patient is to be dosed with our first autoimmune candidate in type 1 diabetes in the coming weeks. We also remain on track to submit the CTA for our second autoimmune candidate by the end of 2026.

Finally, in HIV, we have completed enrollment of additional patients at higher dose cohorts up to 1.2 mg as part of the multiple ascending dose part of the Phase I/II trial. We are analyzing the new data and plan to share results early next year. Overall, we are continuing to execute across our commercial portfolio and pipeline with multiple opportunities to create value for patients and shareholders. And now ask Ralph to share details about our commercial performance. Ralph?

Thank you, Bahija. Today, I will cover KIMMTRAK's continued commercial momentum, our landmark 5-year OS data and our ongoing growth opportunities across melanoma. We delivered $223 million in net sales during the first half of 2026, representing a 16% year-on-year growth and reflecting the sustained strength of KIMMTRAK across our global markets. In the second quarter, we generated $116 million in net sales with the U.S. contributing $75 million and serving as the primary growth driver.

The strong performance was supported by continued demand growth in the community as well as $6 million in inventory stocking by a U.S. distributor. This increase in inventory will create a headwind in Q3.

The fundamentals of the business remain very strong across our 30-plus launch countries. We continue to see over 70% penetration across our major markets and a stable duration of therapy of 14 months. In our fifth year on the market, we expect moderating growth driven by continued commercial excellence, geographic expansion and deeper penetration in the U.S. community setting.

The body of evidence supporting the long-term survival benefit for patients treated with KIMMTRAK continues to build. We presented French real-world evidence showing a median overall survival of 28 months and more recently presented the 5-year survival data from our registrational trial, which I will discuss in Slide 8.

KIMMTRAK's landmark 5-year data sets the bar for overall survival in HLA-A*02:01-positive first-line metastatic uveal melanoma. It is also the longest OS follow-up ever reported in a randomized metastatic uveal melanoma trial and for any T cell engager in a solid tumor. This data shows that treatment with KIMMTRAK doubles the likelihood of survival at 5 years with a 16% OS rate compared with 8% for investigator's choice. Importantly, the survival curve separated early and remained separated over time. In the active arm, 44% of patients alive at 5 years received KIMMTRAK as their only treatment. In the control arm, 87% of patients alive at 5 years crossed over to KIMMTRAK.

Remarkably, only a single patient that did not cross over to KIMMTRAK was alive at 5 years. The 5-year OS benefit of KIMMTRAK was observed across key subgroups, including those with poor prognostic features such as high tumor burden, elevated LDH and extrahepatic disease.

These results clearly demonstrate that starting with KIMMTRAK in first line gives patients the best chance at extending long-term survival. I'm excited about the opportunity to potentially extend this benefit to more patients through our life cycle management program, which I will discuss on the next slide.

Today, we're serving approximately 1,000 patients per year in metastatic uveal melanoma. Our focus now is on scaling this momentum with the potential to expand the number of patients sixfold through our 2 Phase III life cycle management trials. TEBE-AM could transform the lives of up to 4,000 patients with advanced cutaneous melanoma. The data is expected as early as the end of 2026. Our ATOM trial in adjuvant uveal melanoma could help up to 1,200 patients live without their disease. I am confident in our ability to execute on this growth trajectory, and I'm excited about what's ahead for KIMMTRAK and the patients we serve. I'll now hand over to Mohammed to discuss these trials in more detail. Mohammed?

Thank you, Ralph. I'm pleased to be able to share the progress we've made across our pipeline. I will now begin with our 3 registrational melanoma trials, starting with TEBE-AM on Slide 12.

Our lead registrational opportunity is in advanced cutaneous melanoma, where there is high unmet need. No therapy has proven to extend survival in second-line plus cutaneous melanoma following checkpoint inhibitors and targeted therapy, with 1-year overall survival in this setting remaining unchanged at approximately 55%. TEBE-AM is the first Phase III trial aiming to demonstrate an overall survival benefit, the gold standard in this setting. If TEBE-AM is positive, KIMMTRAK would be the first new therapy with an overall survival benefit in second-line plus CM.

As a reminder, first-line patients typically receive either anti-PD-1 with or without additional checkpoints or BRAF-targeted therapy. In second line, patients can switch between these classes where appropriate. Beyond second line, retreatment with prior therapy, chemotherapy and clinical trials remain the primary option.

The only recently approved therapy under accelerated approval in this setting is TIL therapy based on response rates, not overall survival. As a reminder, TEBE-AM is a randomized Phase III trial for melanoma patients who have progressed on checkpoint and if applicable, targeted therapy. Patients are randomized to KIMMTRAK monotherapy, KIMMTRAK plus pembrolizumab or a control arm with the primary endpoint of overall survival. Our confidence in this program is based on multiple considerations, including the promising Phase Ib data showing a 75% 1-year survival rate compared to the historical benchmark of 55% Beyond efficacy, KIMMTRAK is an off-the-shelf therapy with a predictable and manageable safety profile that is already familiar to the melanoma community.

Enrollment is nearing the target of 540 patients with the number of patients left to enroll now in the teens, with top line data still expected as early as the end of this year. Now turning to our second KIMMTRAK-LCM registrational trial. To date, ATOM is the only uveal melanoma registrational trial actively enrolling in the adjuvant setting, where there is currently no approved standard of care. High-risk patients are randomized to either KIMMTRAK or observation with relapse-free survival as the primary endpoint.

The study sponsored by ERTC has been enrolling patients across multiple European countries and is now enrolling in the U.S. Our goal is to bring the benefit of KIMMTRAK to uveal melanoma patients earlier, potentially delaying or even eliminating the onset of metastatic disease. Our third registrational opportunity is also in melanoma, this time with brenetafusp, our TCR targeting PRAME.

The PRISM-MEL-301 trial is a randomized Phase III trial in first-line cutaneous melanoma, comparing brenetafusp plus nivolumab versus either nivolumab monotherapy or nivolumab plus relatlimab with progression-free survival as the primary endpoint. We have now successfully activated over 200 sites globally and are targeting enrollment completion by late 2027.

Next, I will briefly cover the Phase I/II trial with brenetafusp in heavily pretreated patients with advanced melanoma presented recently at ASCO. These data reinforce our belief in the potential of brenetafusp plus nivo in first-line advanced melanoma.

The data demonstrated a 17% overall response rate and a 67% disease control rate with brenetafusp monotherapy at the 160-microgram dose in heavily pretreated patients with advanced melanoma. Relative to the 40-microgram dose, the higher efficacy observed with the 160-microgram dose despite this cohort having less favorable prognostic factors supports selection of this dose for the ongoing Phase III trial in first-line advanced melanoma.

The median overall survival for brenetafusp monotherapy in this late-line melanoma population reached 14.3 months. This compares favorably to other Phase I/II trials of combination therapies in heavily pretreated patients with advanced melanoma, including recent studies with autologous cell therapies. I will now turn to the remainder of our oncology pipeline, starting on Slide 18. Beyond cutaneous melanoma, we are focused on expanding the PRAME franchise into other tumors, specifically ovarian and non-small cell lung cancer. In ovarian cancer, we're building on the monotherapy activity observed in late-line settings by moving into earlier lines of treatment. This includes evaluating brenetafusp in combination with chemotherapy in platinum-resistant ovarian cancer and in combination with bevacizumab in platinum-sensitive maintenance setting. For lung cancer, our efforts remain focused on signal detection of monotherapy across various molecular subsets as well as evaluating combinations with multiple standards of care. We expect to present data from these ovarian and lung cohorts later this year, which will inform next steps.

In parallel, we are advancing our PRAME half-life extended candidate, which is currently in a Phase I dose escalation trial. Our hypothesis for this molecule is twofold. First, to provide patient convenience through less frequent dosing; and second, to potentially increase the overall response rate. As data become available, we will determine the best next steps for the franchise.

The modular nature of our Impax platform allows us to expand our reach beyond oncology and potentially unlock significant growth opportunities in infectious disease and autoimmunity. Last year, we shared preliminary data from an ongoing multiple ascending dose study in people living with HIV.

The data demonstrated a delay in viral rebound after treatment interruption in a small number of patients at higher doses. Since then, we have completed enrollment of additional patients at higher doses, including 1,200 micrograms. We are now in the process of analyzing these data and plan to share an update in the first half of 2027.

Now turning to our third therapeutic area, autoimmunity. Our Phase I trial in type 1 diabetes is now open and actively screening patients, and we expect the first patient to be dosed in the coming weeks. This will be an important milestone, representing our first tissue-specific autoimmune candidate to enter clinical testing. There is high unmet medical need in type 1 diabetes with 50,000 HLA-0201 positive patients newly diagnosed every year.

Our candidate, S118AI is designed to bind to pre-proinsulin, which is expressed exclusively on beta cells of the pancreas. In April, our preclinical data was published and made the cover of science advances, validating the science behind our clinical candidate. We are now turning our focus to our Phase I study that is designed to provide both early evidence of target engagement as well as immune modulation, leveraging a clinically validated endpoint of C-peptide levels.

To recap, we continue to advance a diversified pipeline across all 3 therapeutic areas, anchored by our 3 ongoing Phase III trials in melanoma and a maturing early-stage portfolio. We remain focused on execution as we approach several important data milestones over the coming months. I will now hand the call to Travis to discuss our financial results.

Thank you, Mohammed. Good morning, good afternoon, everyone. Earlier today, we released our financial results for the second quarter and first half of 2026. Please refer to the press release and our latest SEC filings for our full financial results. Let me share some of our key financial highlights from the quarter and provide some commentary on expectations for the remainder of the year. We are pleased to report continued strong performance for KIMMTRAK, with second quarter net sales reaching $116 million. This represents an 18% increase over Q2 of 2025.

Looking at the geographic breakdown for the quarter, the U.S. contributed $75 million, up 17% year-over-year, while Europe reached $34 million and our international regions grew to $7 million. As Ralph mentioned, it is important to note that Q2 sales in the U.S. were partially influenced by wholesaler stocking of approximately $6 million. If you normalize for the stocking, our underlying quarterly sequential growth was 3%. This is in line with our expectations for moderating sales growth moving forward given our high market penetration.

Moving to expenses. Our R&D spend for the quarter was $74 million compared to $69 million in the prior year. This increase was primarily due to advancement of our clinical programs, including our 3 Phase III trials. As we look ahead, we continue to expect R&D expenses to modestly increase year-over-year, although at a slower rate than in 2025.

Turning to SG&A. This quarter's expenses were $44 million, up marginally from $43 million in Q2 of last year. We will continue to be disciplined with our SG&A spend and may incur incremental increases in these investments as we prepare for the potential expansion of KIMMTRAK into cutaneous melanoma. This quarter, we had a net loss of just under $1 million, an improvement versus the $10 million loss in the same period of last year.

Our balance sheet remains exceptionally strong. As of June 30, we held $880 million in cash and marketable securities. This is an increase of $16 million since the beginning of the year. One last item to note is we expect to pay approximately $120 million in sales-related rebates during the second half of this year. This amount is higher than in prior years due to our revenue growth in Europe and the completion of the pricing agreement with France in early 2025, which resulted in rebates from revenue generated in the prior 5 years being payable this year. As a reminder, these rebates impact cash only.

Moving forward in 2027, we expect these rebate payments to return to similar amounts as paid in 2025. Our strong balance sheet provides the flexibility to support near-term commercial execution and pipeline advancement while continuing to invest in longer-term growth opportunities across our business. I'll now turn the call back to Bahija.

Thank you, Travis, and thank you, team. The 5-year overall survival data with KIMMTRAK confirms that what it can deliver for HLA-A2-positive patients with MUM, while also confirming the potential of our Impax platform. We look forward to sharing the TEBE-AM data as early as the end of 2026, which could offer a much needed treatment option for patients with advanced cutaneous melanoma. Our teams are working to enroll our multiple ongoing clinical trials to deliver data for our other candidates through 2026 and beyond. Behind all of this work are patients, the one alive today because of KIMMTRAK and the many more we intend to reach.

Thank you to all our patients, their families and our employees. Thank you for your support. And now we'll be very happy to take your questions.

[Operator Instructions] Our first question today is coming from Tyler Van Buren from TD Cowen.

For the TEBE-AM trial, can you please review the study plan for us with respect to the potential interim or interims and a final analysis? Specifically the potential top line readout that is possible by year-end, I assume that must be the first interim OS analysis considering that enrollment is not completed? Or am I wrong there? And can you help us understand how that is powered? And if there is an interim in the final, how that's powered relative to the final?

Mohammed, do you want to take that?

Yes. So just as a reminder, we don't usually get into the specifics of the stat plan, but it's not unusual in a trial like this to have interim analysis designed into. But just because there is an interim analysis written to the protocol doesn't mean that you have to actually execute on it.

And you're correct, the way the trial was designed, we don't do any data analysis until enrollment is complete. And we are still on track, as we've said before, that the earliest possible readout of the headline data can be as early as the end of this year. So we remain on track for that.

Our next question is coming from Michael Yee from UBS.

This is Dina on for Mike. I know that you guys are not yet enrolling the second-line melanoma trial, and I think guidance is first half, so maybe just getting maybe a month or so behind. But just thinking about the timing is still reiterated for year-end. I mean, is there any risk that this can fall into 2027? And if it does, can we presume that the KIMMTRAK arms are potentially doing better versus the control arm? I guess on the control arm also, what percent of the patients do you think would be on a clinical trial versus chemo or IO retreatment?

Okay. Since you have 2 parts, I think you can take it, Mohammed.

Sure. Happy to take those 2 questions. So with regards to your first question, it's important to remember that regardless -- especially for the patients that are being enrolled now, they typically have very minimal impact on the primary endpoint, which is event-driven and its overall survival. So that's the reason why we're still reiterating that -- the earliest possible readout can be as early as the end of this year. With regards to the control arm and the possibility of clinical trials, both based on our real-world evidence and sort of the experience so far in the composite trial, not by any specific arm, the use of clinical trials is very low, typically in the single-digit percentage.

Our next question today is coming from Eric Schmidt from Cantor Fitzgerald.

This is [ Imogen ] on for Eric. For the shape of the enrollment curve for TEBE-AM, could you just provide a little bit more color on that and how that could lead to the event rates being hit maybe for an interim or a final analysis later this year? And then as we think about the half-life extended PRAME data coming, could you help us think about expectations there and which data sets from would be reasonable to compare that to?

Happy to take that. So with regards to the TBM enrollment curve, once we reach -- this is -- I'm just giving you sort of a general experience, right? Once you reach sort of all the sites are activated, then you basically have steady-state enrollment, and that's been our experience with the ongoing TEBE-AM trial. And as I mentioned a little bit earlier, these last patients, even though there's a few weeks delay, these last patients typically don't have any impact. The impact usually comes from patients that have enrolled much earlier on the PRAME endpoint. So that's why we're reiterating that the headline data could be as early as the end of this year.

With regards to the PRAME+HLE study, this is -- as a reminder, this is a Phase I trial that's been ongoing. So escalation continues. And so depending on where we get to, we always have said that we share data once we have a complete story. So depending on how that data evolves, we look forward to sharing that. With regards to comparisons with brene, so many of the sites that are on the half-life extended were on the brene trial and many of the patient types that were enrolled in brene are being enrolled in the PRAME+HLE, namely melanoma and ovarian. So that's -- so those are probably the tumor types that you'd look forward to trying to compare across the 2 trials.

Yes. And I will just add that the molecule is almost exactly the same, except for the Fc portion basically for extended half-life and it's the same peptide. So that's why.

Our next question today is coming from Jessica Fye from JPMorgan.

This is on [ Tanmay ] on for Jess. I had a couple of questions on KIMMTRAK. In terms, so we saw KIMMTRAK U.S. revenues grew 17% year-on-year to $75 million. So does that 17% growth rate fall under your definition of moderate growth that you have repeatedly referred to? And where does the U.S. and Europe penetration stand today for KIMMTRAK? And if you could provide additional color on split between the academic centers and community-driven penetration in the U.S., that would be great.

Great. So you were cutting off. So I hope we understood the question. I think there are several parts of the question. So one is on the 17% in the U.S. is just the moderation, and then you can take the next one.

Yes, I'm happy to start, and apologies if I don't answer your question directly, you were breaking up, but I'm going to do my best to interpret what you asked. I think you asked about the 17% growth being considered moderate. I think one of the things that look, that's year-on-year growth. So one of the things to consider is given we're on the fifth year on the market and have very high penetration across all major markets, we've seen our quarterly sequential growth moderate, and that's what we mainly refer to when we're seeing moderating growth.

The penetration in the U.S. versus Europe?

Just a comment on the 17%, Travis. The part of that what contributed to the 17% is a stocking -- unusual stocking event that we had in the U.S. of about $6 million. So this is why you're seeing also this higher number than what we expect to be moderating. With regard to penetration and the reason why we believe this is moderating is because we're above 70% penetrated in the U.S. That includes 70% of our prescriptions coming from the community. And in countries in Europe, we're about 75%, 80%. So very well penetrated across all major markets.

Our next question is coming from Jack Allen from Baird.

I wanted to ask on TEBE-AM. I appreciate that you're still enrolling the final patients in the study and that they might not have an impact on the analysis that could occur as early as late '26. I did want to ask how you're coming up with the late '26 kind of comment here. Are you looking at any blinded event rates in the study? And how are those trending? Any qualitative comments would be helpful.

Mohammed, do you want to take that?

Yes. Happy to take that question. So you're correct. I mean that's very standard as you get close to enrollment completion and looking forward to potential analysis, but there is a separate independent stats group that's looking at the combined event rate. And so based on that information, that's how we're guiding to that we could have headline data as early as the end of '26. As we get closer to that, we can certainly provide an update because the zone of uncertainty becomes more narrow.

Our next question is coming from Sean Laaman from Morgan Stanley Investment Management.

Just looking ahead on TEBE-AM and advanced cutaneous melanoma to the commercial opportunity. So what proportion of the estimated HLA-positive patient base do you think you could realistically access, say, within the first 3 years of launch?

Sean, the opportunity here is up to 4,000 patients across U.S. and EU, and this is HLA-021 positive patients. I think from a modeling perspective -- and this is obviously very much dependent on the data itself because this is an area of high unmet need. There's little too therapies approved in this setting.

And we would be the first off-the-shelf OS-driven therapy. So I expect a good uptake, especially since we're building from our base where currently 50% of patients with cutaneous melanoma are being treated by physicians experience with KIMMTRAK. So we expect a good uptake based on our incremental impact today.

Our next question today is coming from Eva Fortea from Wells Fargo.

. A quick one from us on KIMMTRAK. Are you seeing patients getting diagnosed a little bit earlier in disease driven by availability of KIMMTRAK now for 5 years in the market? Or are the numbers still what you were expecting 5 years ago?

The numbers that we're seeing today, actually, we have seen some improvement when it comes to monitoring. Keep in mind that before KIMMTRAK there was nothing available for these patients. So oftentimes, physicians saw no benefit of having very continuous intense monitoring. Nowadays, we've shown with KIMMTRAK and in fact, you've seen in our data that patients with lower tumor burden, as you'd expect with many therapies and especially immunotherapies do extremely well. The hazard ratio for these patients was 0.36. So we do see a little bit of a more systemic monitoring of these patients more so than we could see before, and this is across most countries.

Our next question is coming from Graig Suvannavejh from Mizuho.

This is Doug on for Greg. Quick one on the brenetafusp Phase I/II studies in ovarian cancer and non-small cell lung cancer. Just sort of like what you should be expecting to come from that data? How robust the data sets? Are these like ORR numbers that are really going to help you sort of choose what indications to pursue in advance? And then first part of the question, then as a follow-up on brenetafusp, specifically in melanoma, since the half-life extended version is so comparable, like let's say they're both successful in melanoma, how do you expect to manage that? Would they compete with each other? Would have-if extended, if all goes according to plan, sort of replace brenetafusp? Or would they like go after different populations? Or is it just way too early to tell?

Happy to take on the 2 questions. With regards to the expected ovarian and lung data from the Phase I/II trial, with ovarian, we already saw an initial signal in late-line platinum-resistant ovarian cancer about 2 years ago. So we're building on that. So there should be 2 parts to that. One is longer follow-up of that original monotherapy cohort, so we can look at survival, which was not mature 2 years ago.

And since then, we've pivoted to earlier lines and are looking at combinations with standard of care, especially bevacizumab in the platinum-sensitive maintenance setting. But this will be a safety size cohort where we're looking at initial safety and feasibility, but also we'll have the ability to look at initial clinical activity. With regards to lung, we're still signal seeking, but the monotherapy cohort in terms of size would be similar to what we shared with ovarian and melanoma, but across multiple molecular subsets. As you know, lung is quite heterogeneous. And then we have safety size cohorts with standards of care within lung. With regards to the HLE question, I think it's still too early to tell, but the way we're thinking about this is that, obviously, brenetafusp is already in the frontline PRISM+MEL trial for the convenience basically it's frequent dosing.

Right, so in the PRISM+ MEL trial even through the phase 1, 2 development with brene was week given it's now combined with study, and we have full confidence in that trial. HLE, because it at minimum offers patient convenience, could certainly be positioned for earlier lines of therapy where that becomes important, such as adjuvant setting. And then, of course, there are other diseases like ovarian and lung that we haven't, we're going to compare the data to help guide next steps.

Do you want to comment on what we built in, in the trial, in the PRISM trial for the convenience, basically, this frequent dosing? Right. So in the PRISM trial, even though the Phase I/II development with brene was weekly, given it's now combined with nivolumab, the way the trial is designed is after the first 3 months of weekly dosing, it switches to biweekly dosing. And then after a year, it switches to monthly dosing. So that's built into the pivotal trial from a patient convenience perspective. .

Our next question today is coming from Romy O'Connor from Kempen.

I have a question on the sales-related rebate accruals. So of the $120 million, I just wanted to ask if you could clarify what drives the size of payments. And going forward, how should we think about the normalization here in terms of cadence maybe?

Yes. So 2 things have contributed to the rebate payments that we expect to make in the second half of this year. One is our sales in Europe have been growing. And two is the pricing agreement with France that we struck in early 2025, which allotted for cash rebate payments being made over rebates that have been accrued in the prior 5 years in the second half of this year. So that's why you're seeing a higher number in the second half of this year. Moving forward, we'd expect that those rebate payments in 2027 to return back to more similar levels to what we paid in 2025, which was in the $65 million to $70 million range.

Our next question is coming from Jeff Jones from Oppenheimer.

Quick one regarding the AACR results and the 5-year over survival. Do you expect that to have any impact on duration of therapy, which I believe sits around 14 months for KIMMTRAK right now?

Jeff, thank you for the question. I'm very excited about these 5-year results. Obviously, this is the first time that we talk about 5-year survival in this disease. So clearly, KIMMTRAK is transformation for a lot of these patients. The 5-year results themselves will probably not have an impact, but it allows us to see certain aspects of why we have a 14-month duration of therapy.

So for instance, 44% of patients alive at 5 years only saw KIMMTRAK as their treatment. So that speaks to the safety, the long-term safety and the fact that a lot of the efficacy that we're seeing in these curves is driven by KIMMTRAK. And this is something that we're -- the team is leveraging, especially when it comes to conversations, including sometimes in conversations on treatment beyond progression.

So we will reinforce that message, but obviously, we don't expect necessarily to drive the 14 months beyond what we've seen because it's been stable for the past few quarters.

The 14 months are already much higher than what we've seen in clinical trials, which tells you again how KIMMTRAK is really being successful in the market.

Our next question is coming from Faisal Khurshid from Jefferies.

This is Gabriel dialing in for Faisal Khurshid. Can you speak about the extent to which you see [ IDEA's ] oral regimen as a competitive risk to KIMMTRAK in uveal melanoma? They've spoken about potentially getting HLA-positive patients into their initial label. And if they do, how do you think about the impact to the KIMMTRAK business?

Look, I think this is good news for HLA-021negative patients, which currently still have a very significant unmet need because they're not eligible for KIMMTRAK. On the other side, for HLA-021pitive patients, KIMMTRAK is the standard of care across all major markets. This is underpinned by 5-year overall survival data that we just discussed and really a safety that's quite exceptional. And again, we discussed patients being on treatment for a long time. So from a value proposition perspective, with KIMMTRAK you're getting OS, you're getting safety that's tolerable for years. So I see KIMMTRAK being very much anchored in first line.

Our next question is coming from Rajan Sharma from Goldman Sachs.

I just wanted to follow up on some of the comments on brene. So I was just wondering if you could discuss your internal bar in ovarian cancer in the context of all the ADCs that we're seeing in development there as well as the immatics data that we saw at ASCO. What would you need to see to progress development in this setting?

I would say that the growth of ADCs in ovarian cancer highlights the unmet need in this disease. With regards to ADCs, our view is that ADCs are essentially targeted chemotherapy. And our platform has a unique mechanism, and there's no reason to expect that why you couldn't combine the 2. We've certainly shown in the clinic we can combine with chemotherapy.

With regards to our internal bar, I think the general approach is that you want to generate data in the intended target population, which we're doing in the brene-101 study, i.e., the maintenance trial. And then you want to look for an effect size on a relevant clinical endpoint that would justify the next stage of investment. So we are looking forward to sharing that data later this year, and that will help guide the next steps.

Our next question today is coming from Patrick Trucchio from H.C. Wainwright.

This is Luis in for Patrick. I was wondering for your ImmTAV platform and the HIV data, you say you have it at hand and you're analyzing it, and you're planning to present the results from that analysis early in 2027. Should we assume that's going to be at the CROI conference like last year? And what data should we expect there? And are you in any potential partnership discussions regarding that platform in general?

A good assumption. I think -- so we try always to share data in a conference. So that's our goal. We always talk inside and outside on data. But there was another one, I think, in the question.

What to expect for the data?

Yes. So that's basically, as we presented the multiple ascending dose last time, we definitely have not reached -- we saw a start of a dose response, and we didn't reach a DLT, if you will. So we were going up with the dose. And now as we said, we will have data for 600 and 1.2 milligrams of data. So that's what we will be sharing in the same fashion that we did for the first MAD data.

Our next question is from Jack Hallen from Baird.

I wanted to ask about something that I heard from a KOL recently that we were discussing the utilization of KIMMTRAK in the first-line uveal melanoma setting. They alluded to a lot of their patients receiving ctDNA monitoring for response. And obviously, you've seen a pretty durable duration of treatment of 14 months in the commercial setting. I'm just curious, to what extent in your conversations with physicians, are they monitoring ctDNA -- because I know progression can occur on the drug, but ctDNA really seems to be the indicator of response and benefit?

Yes. Happy to take that. I think if I step back, the utilization of ctDNA was data that Immunocore pioneered with our translational medicine work, and we published that for both -- for our pivotal Phase III trial showing that it looked as a better surrogate than even RECIST response for predicting long-term outcome. In our conversations with physicians, I think it varies. So institutions that are more academic and have access to either an in-house one or they can utilize commercially available ctDNA.

We definitely see that they will leverage this to help guide treatment decisions. Others are using it in a setting where a patient has been on therapy for a long time, multiple years. And if the ctDNA clears, they're even -- they're using that as a guide to how to manage the patient. So we see it based on the expertise of individual investigators and institutions and access to ctDNA.

Which I think we have to say we have patients 5 years, 6 years, 7 years, which was completely unheard of. So really happy with that.

Thank you. We've reached the end of our question-and-answer session. I'd like to turn the floor back over for any further or closing comments.

All right. Thank you very much. I really would like on behalf of the team to thank you for your questions and thank our shareholders for their support. So thank you very much.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

Greetings, and welcome to the Immunicore conference call and webcast. [Operator Instructions] Please note that this conference is being recorded. I will now turn the conference over to Morgan Morse, Investor Relations. Thank you, Morgan. You may begin. .

Thank you, Darryl. Good morning and good afternoon. Thank you for joining us on our Q4 and full year 2025 earnings call. During today's call, we will make some forward-looking statements, which are qualified by our safe harbor provision under the Private Securities Litigation Reform Act of 1995. Please note that actual results can vary materially from those indicated by these forward-looking statements, including those discussed in our filings with the SEC. .

On today's call, I am joined by Dr. Bahija Jallal, CEO of Immunocore, who will share our 2025 overview and achievements; Ralph Torbay, Head of Commercial, will review our Q4 and full year KIMMTRAK results; Mohammed Dar, our Chief Medical Officer, will provide a pipeline update including our ongoing registrational [ late line ] cutaneous melanoma and other highlights across our pipeline. And finally, Travis Coy, our CFO and Head of Corporate Development, will provide some key highlights from our financial results reported earlier this morning. I will now turn the call to Dr. Bahija Jallal.

Thank you, Morgan. Good morning, and good afternoon, and thank you all for joining us. 2025 was a year of consistent execution across every part of our business. I am pleased to share our results and where we're headed as we continue to deliver on our mission. For the year 2025, we generated $400 million in net revenue from KIMMTRAK, up over 29% from the prior year. .

KIMMTRAK is now approved in 39 countries and launched in 30 markets. Growth continues to be driven by deeper U.S. community penetration and continued global expansion. Real world duration of therapy is now 14 months, exceeding our clinical trials experience. Before KIMMTRAK, patients with uveal melanoma diagnosis were given 12 months or less to live. Now with KIMMTRAK, it's not unusual to see patients living 3, 4, 5 years or more. This is why we're here, and this is why we come to work every day.

But we're not stopping here. To reach even more patients, we're expanding the reach of KIMMTRAK through a robust life cycle management program with 2 Phase III trials. TEBE-AM in second-line cutaneous melanoma enrollment on track for the first half of 2026 completion. ATOM in adjuvant uveal melanoma enrolling across multiple sites in Europe and planning to open sites in the U.S. in 2026. This is, to our knowledge, the only active Phase III in this setting. Beyond KIMMTRAK, we have our third Phase III trial. PRISM-MEL-301 with brenetafusp in first-line cutaneous melanoma. The IDMC has selected the 160-microgram dose, which is the highest dose in the last December.

We are also expanding our oncology platform beyond melanoma into ovarian and lung, colorectal cancer and GI cancers. Mohammed will share more details later. And then beyond oncology, we presented promising data for our HIV functional cure program at CROI and our hepatitis B candidate showed encouraging Phase I results at ASLD confirming the potential of our platform in infectious disease.

In autoimmune diseases, we submitted the CTA for our type 1 diabetes program and expect to dose the first patient in the Phase I in the first half of 2026. Our balance sheet remains strong at approximately $864 million in cash, providing the flexibility to advance the pipeline. I'll now ask Ralph to share more about our commercial performance. Ralph?

Thank you, Bahija. Today, I will walk us through KIMMTRAK's full year results and growth opportunities across melanoma. 2025 has been another year of strong commercial execution, marking this our 15th quarter of growth. KIMMTRAK generated $400 million in net revenues for the year, representing 29% year-on-year growth. This sustained performance reflects KIMMTRAK's position as the global standard of care in first-line metastatic uveal melanoma with over 70% penetration across all major markets.

This breadth of adoption is a testament to KIMMTRAK's transformative long-term impact, with one in 4 patients alive at 3 years, an unprecedented milestone in this disease. Mean duration of therapy remains impressive at 14 months, as Bahija mentioned. Continuing the theme of KIMMTRAK's delivering exceptional results, we recently presented real-world data at ESMO IO from 150 patients, showing a median overall survival of 28 months.

We plan to build upon this data with the U.S. real-world evidence to be published this year. We also expect to share the 5-year overall survival from our registrational clinical trial which will further support KIMMTRAK's long-term benefit. Now as we enter our fifth year on the market, we expect moderating growth through continued commercial execution, further global expansion and increased penetration in the U.S. community setting.

Speaking of the community, KIMMTRAK's adoption is widespread as evidenced by 70% of all KIMMTRAK prescriptions come from the community. Half of all patient starts happen in the community. And in 2025 alone, we activated 150 new accounts, most in the community. This broad adoption is important because it speaks to KIMMTRAK's value proposition of unprecedented survival and manageable safety.

It also brings KIMMTRAK closer to home for many patients who live in less dense geographic areas. Lastly, it creates a wide foundation for a potential next indication where half of all patients with cutaneous melanoma are treated by physicians experienced with KIMMTRAK. I'm very excited by KIMMTRAK's midterm growth potential. Today, we're serving approximately 1,000 patients per year in metastatic uveal melanoma, which delivered $400 million in net sales in 2025.

When you look across the horizon, the opportunity is up to sixfold larger with our 2 Phase III life cycle management trials. The first one TEBE-AM, the only randomized Phase III study in advanced melanoma with an overall survival endpoint that could transform the lives of up to 4,000 patients. Second, ATOM, in adjuvant uveal melanoma that could help up to 1,000 additional patients. I'm confident in our ability to execute on this growth trajectory, and I'm excited about what's ahead for KIMMTRAK and patients we serve.

I'll now hand over to Mohammed to discuss these trials in more detail as well as our expanding pipeline.

Thank you, Ralph. I'm delighted to join this executive team and look forward to sharing the developments across our clinical programs. At Immunocore, we have built a truly unique and diversified TCR pipeline that now spans 3 therapeutic areas, and I'm pleased to walk you through our progress today. Our R&D engine has delivered a robust portfolio anchored by 3 ongoing Phase III trials in oncology with data readouts beginning as early as the second half of 2026, with TEBE-AM.

Beyond our late-stage efforts, we look forward to new insights maturing this year across our early-stage oncology and infectious disease programs. In autoimmune, 2026 marks a pivotal milestone for our platform as we initiate our first clinical experience. I'll now begin by highlighting our 3 registrational melanoma trials, starting with TEBE-AM. Our first opportunity is in advanced cutaneous melanoma, where there is a high unmet need. No therapy has been proven to extend survival in the second plus cutaneous melanoma setting, falling checkpoint inhibitors and targeted therapy. 1 year overall survival in this setting is approximately 55%.

In first-line patients receive either anti-PD-1 with or without additional checkpoints or BRAF-targeted therapy. In second line, patients can switch between these classes where appropriate. Beyond second line, there remains a large unmet need: chemotherapy, retreatment with prior therapies and clinical trials remain the primary options. The only new therapy approved in this setting is TIL therapy, which was based on response rate under accelerated approval, not overall survival.

TEBE-AM is the first Phase III trial aiming to demonstrate an overall survival benefit, the gold standard in the population. If TEBE-AM is positive, KIMMTRAK would be the first new therapy with overall survival benefit in the second line plus cutaneous melanoma setting. As a reminder, TEBE-AM is a randomized Phase III trial for melanoma patients who have progressed on checkpoint and, if applicable, targeted therapy. Patients are randomized to KIMMTRAK monotherapy, KIMMTRAK plus pembrolizumab or a control arm with a primary endpoint of overall survival.

Our confidence in this program is supported by promising Phase Ib data showing a 75% 1-year survival rate compared to the 55% benchmark. Beyond efficacy, KIMMTRAK is an off-the-shelf therapy with a predictable and manageable safety profile that is already familiar to the melanoma community. We remain on track and project to complete enrollment in the first half of 2026, with top line data expected as early as the second half of this year.

Now turning to our second registrational trial. ATOM is the only active registrational Phase III trial in the adjuvant uveal melanoma setting, where there is currently no approved standard of care. High-risk patients are randomized to either KIMMTRAK or observation with recurrence-free survival as the primary endpoint. The study sponsored by the EORTC is currently activated across multiple European countries and is expected to begin site activations in the U.S. during the first half of 2026.

Our goal is to bring the benefit of KIMMTRAK to patients earlier, potentially delaying or even eliminating the onset of metastatic disease.

As evidence of our robust R&D engine, we now turn to our third registrational opportunity with melanoma, this time, leveraging our TCR targeting PRAME known as brenetafusp. PRISM-MEL is a randomized Phase III trial in first-line cutaneous melanoma, comparing brenetafusp plus nivolumab versus either nivolumab monotherapy or Opdualag, with progression-free survival as the primary endpoint. .

In November 2025, in line with the FDA's project OPTIMIST, the IDMC completed the dose selection process choosing the highest dose to move forward. We have successfully activated over 200 sites globally and are targeting enrollment completion in 2027.

I will now outline how we are strategically applying our platform to address a broader range of high unmet need tumor types. Beyond cutaneous melanoma, we are focused on expanding the PRAME franchise into other tumors, specifically ovarian and non-small cell lung cancer. .

In ovarian, we are building on the monotherapy activity observed in late-line settings by moving into earlier lines of treatment. This includes evaluating brenetafusp in combination with chemotherapy in platinum-resistant ovarian cancer and in combination with bevacizumab in the platinum-sensitive maintenance setting. For lung cancer, our efforts are focused on signal detection across various combinations, including chemotherapy and [ osimertinib ]. We expect to present the data from these ovarian and lung cohorts in the second half of 2026, which will inform next steps.

In parallel, we are advancing our PRAME half-life extended candidate, which is currently in dose escalation. Our hypothesis for this molecule is twofold: first, to provide patient convenience through less frequent dosing; and second, to potentially increase the overall response rate. We expect to have a comprehensive data package by the second half of 2026 to determine the optimal path forward for the franchise.

The modular nature of our platform allows us to expand our reach beyond oncology and unlock significant growth opportunities in infectious disease and autoimmune. At CROI early last year, we presented initial data from 16 patients enrolled into the multiple ascending dose portion of our HIV study. The data were very well received by investigators and 2 important findings emerged. First, the treatment was well tolerated. And second, we observed a dose-dependent antiviral effect.

At the 60-microgram target dose, you can see that when we stop both our compound and the anti-retroviral regimen, viral rebound occurs rapidly. However, at the 120 and 300-microgram target doses, we observed a delay in viral rebound. Note the orange lines, providing preliminary clinical evidence that we are impacting the viral reservoir, which is the critical first step toward achieving a functional cure. The clinical data gathered so far confirms the potential of our platform in infectious disease. We are continuing to evaluate higher doses in this study, and we expect to have data from the ongoing dose escalation in the second half of 2026.

Now turning to our third and newest therapeutic area. Our vision for treating autoimmunity is unique. We aim to achieve tissue-specific down modulation of the immune system, thereby avoiding the risks associated with systemic immune suppression, which is the current approach taken in the field. We are currently advancing 2 autoimmune candidates. The first is S-118i, which targets the beta cells in the pancreas in patients diagnosed with type 1 diabetes. The second is U120AI, which targets CD18 on Langerhans cells, specialized antigen presenting cells in the skin for the treatment of atopic dermatitis.

Today, I'm going to focus on our type 1 diabetes program, which represents the first clinical test of our tissue tethered PD-1 agonist approach. We chose type 1 diabetes because of the profound unmet medical need with 50,000 patients newly diagnosed every year and data supporting the role of T cells as one of the key mediators of the disease. Our candidate S118i binds to pre-proinsulin, which is expressed exclusively on the beta cells of the pancreas.

We have already generated compelling ex vivo proof-of-concept data using pancreatic slices from human donors. We demonstrated that S118i binds specifically to beta cells, as shown in the middle panel and successfully rescue them from T cell-mediated killing as seen in the graph on the far right. Importantly, these rescue beta cells remain functional and continue to secrete insulin.

Following our CTA filing in December 2025, we are now poised to move into the clinic this year. Our Phase I study is designed to provide early evidence of target engagement and immune modulation. So to recap, we have a robust, diversified pipeline with important readouts later this year, and our R&D teams remain focused as we continue to advance our platform across all 3 therapeutic areas.

I will now hand the call to Travis to discuss our financial results.

Thank you, Mohammed. Good morning, and good afternoon, everyone. Earlier today, we released our financial results for the fourth quarter and year ended 2025. Please refer to the press release and our latest SEC filings on Form 10-K, our full financial results. Let me share some of our key financial highlights for 2025 and then touch upon our expectations for 2026. We are pleased to report strong performance for KIMMTRAK with full year net sales reaching $400 million. This represents a 29% increase over 2024 with volume-driven growth across the U.S., Europe and international regions. Looking ahead to 2026, as we enter KIMMTRAK 5th year on the market with significant penetration across all major markets, we naturally expect growth to moderate. Our underlying sequential quarterly revenue growth has been in the range of 4% to 7% the last few quarters.

We are seeing that growth slowdown and expect that trend to continue in 2026. Moving from revenue to expenses. As we continue to maximize global access to KIMMTRAK and advance our pipeline, our operating expenses increased. The increase in our R&D spend versus last year was primarily driven by ongoing investments in our 3 Phase III trials and by advancing our earlier stage programs, including preparations to initiate clinical studies with our autoimmune candidates.

In 2026, as we continue to invest in our pipeline, we expect R&D expenses to increase modestly year-over-year, although at a slower rate than they did in 2025. Turning to SG&A. 2025 expenses were marginally higher versus 2024 as we remain disciplined with this spending. In 2026, we expect only incremental increases to these investments, driven by commercial preparations for the potential expansion of KIMMTRAK into cutaneous melanoma.

Overall, we are pleased to have reduced our operating loss in 2025 as revenue grew more than our operating expenses. Our balance sheet remains exceptionally strong. As of year-end, we had $864 million in cash and marketable securities, an increase of more than $40 million versus last year. Our robust financial position, combined with data-driven investments and expense discipline, provides us with the flexibility and resources to continue advancing our mission of delivering transformative medicines to patients. I'll now turn the call back to Bahija.

Thank you, Travis, and thank you, team. Four years ago, we launched the first ever approved therapy for metastatic uveal melanoma. Today, we're a commercial stage biotech with a validated platform, 3 Phase III trials and we're expanding into infectious disease and autoimmunity. We're not just treating cancer. We're also redefining what's possible with T cell receptor biology.

2025 was a year of execution and 2026 will be a year of data and continued progress. We thank you all for your support. And now we'll be happy to take your questions. Thank you.

[Operator Instructions] Our first question comes from the line of Michael Yee with UBS. .

Congrats on the progress. I have a quick question on TEBE-AM. I think that's a really exciting opportunity and the data is coming soon. Can you remind me the general geographic breakdown of your enrollment. Is it half U.S. or Europe, et cetera, et cetera, because I think there's much more limited agents outside the U.S. and that could impact the control arm. And secondly, you are designed KIMMTRAK and also KIMMTRAK plus PD-1. Did you go through a DSMB analysis or a look to test that KIMMTRAK alone is probably doing at least as good as the combo and what insights did you have on that?

Great. Mohammed, do you want to take that? .

Sure. Thanks, Michael, for the questions. With regards to enrollment on TEBE-AM, the majority of our enrollment is coming from Europe, in line with other recently completed pivotal trials. We expect between 10% and 15% from U.S. and then the rest from the remaining countries. With regards to your question around DSMB and whether we had them look at activity within mono versus combo as you recall, the original TEBE design was a Phase II/III design. Based on enrollment metrics, we converted it all into a Phase III seamless -- a single consolidated trial design. We've never looked at the data, neither did the IDMC. So this is based purely on enrollment metric. And as a result, we saved 1 year in terms of the conduct of the Phase III trial.

Our next question comes from the line of Tyler Van Buren with TD Cowen.

Just another on TEBE-AM, given how important the readout is in the second half. Can you just remind us what both treatment arms are powered for an overall survival and what you believe the likelihood is that the monotherapy arm in addition to TEBE plus pembro combination could succeed.

Thank you for the question, Tyler. So with regards to the statistical assumptions, we usually don't get into the details, but it's fair to say that we are -- we've designed the study to basically meet both a statistically significant and clinically meaningful threshold difference from the control and that, in my experience, on average, that's at least a 30% difference from the control.

With regards to assumptions between mono and combo, again, we typically don't get into like are detailed at the statistical plan, but needless to say, our data from 201 was based on combo. So certainly, logic would support like the combo may outperform the mono, but that's what I can say.

Our next question comes from the line of Eric Schmidt with Cantor Fitzgerald.

Maybe to switch gears a little bit toward Ralph and Travis. It feels like we've been talking about or guiding to a deceleration in contract sales for years now, yet growth has been pretty robust as you guys called out 25-ish plus percent year-on-year.

I hear you, Travis, you're thinking that quarterly growth rate is going to come down from 4% to 7%. Do you have value in mind that you think is realistic that is substantially less than 25%.

Eric, thanks for the question. Obviously, we're pleased that we continue to overperform commercially. So we're excited about that. And we're now entering the fifth year on the market, so we do naturally expect that growth to begin to moderate with significant penetration across all major markets, both U.S. and in Europe. One thing to keep in mind, that year-on-year growth of 29%. We did have some rebate reserves in 2024 and 2025. If you normalize for those rebate reserves, our underlying growth was around 20%. So I just offer that up as a reminder to folks. So you have a little bit of better understanding of where we expect the growth to moderate from.

And I see you operate around cash flow breakeven in 2025. Is that a reasonable estimate for '26?

Yes. We continue to focus on investment in our 3 Phase IIIs. And so we do expect R&D expenses to modestly increase into 2026 from 2025. From an SG&A perspective, we've been really pleased with how well we've managed those expenses and continue to be disciplined on that front. We've been very consistent really over 2024 and 2025 around that $40 million mark per quarter and only expect incremental increases into 2026 as we prepare for cutaneous melanoma.

Our next question comes from the line of Jack Allen with Baird.

Congrats to the team on the update. I wanted to ask a little bit on the commercial outlook. Pending positive results in the TEBE-AM study, I wanted to ask the team how they thought about pricing in that indication. I know you have a very meaningful price in metastatic uveal melanoma, which is a rare space. How do you think about the larger second-line cutaneous melanoma market and any impact on price moving forward there, pending a launch into that indication?

Thanks, for the good question. So when you consider the unmet need that exists today in advanced melanoma. And the fact that we have a Phase III with an overall survival end point and the fact that we're -- we haven't established safety and this is an off-the-shelf treatment. Really, if the data is positive, and this is all data dependent, we believe that we can potentially defend that price appropriately given the OS endpoint, of course, data dependent.

Our next question comes from the line of Sean Laaman with Morgan Stanley.

I have a question on your autoimmune entry, so first candidate entering Phase I in 2026. How do you evaluate our success in the early autoimmune studies relative to oncology benchmarks? And how capital-intensive could the platform become?

Yes. So thank you for this question. I'll take that. We chose type 1 diabetes exactly for that reasons that we can determine very early on if 2 questions that will answer right away, does the drug bind the target and that we will look at that with the soluble PD-1, for instance, and other things.

And the second is we do have the surrogate C peptide that we can measure. Once we have the dose, we can measure that, and that's a surrogate for efficacy. So exactly that we can find out basically early on if this has the potential to be active or not. And that's really the reasoning before we engage into big Phase IIbs or something like that.

Our next question comes from the line of Jonathan Chang with Leerink Partners.

How are you thinking about the learnings from the success of KIMMTRAK in uveal melanoma? And how could those apply to a potential commercial launch in cutaneous melanoma, what similarities and differences are you considering?

Yes. Great question. Ralph, do you want to take that?

Sure. Jonathan, thank you for the question. So -- we -- in cutaneous melanoma, you have half of these physicians treating patients who -- half of the patients with cutaneous melanoma are being treated by physicians who are experienced with KIMMTRAK today. So this is a great foundation upon which we will build. In addition to that, the team is very well trained, has executed recently in the launch and has a track record of successful launches. So all of this together will lead into, I think, a good data dependent, of course, potential launch.

A strong medical team. I think that's following with the science.

Our next question comes from the line of Greg Suvannavejh with Mizuho Securities.

I was curious about your PRAME portfolio, you've got several different programs going on there. And I'm wondering, you've got a lot of combinations for lung cancer and also ovarian cancer. I'm wondering what are the different scenarios that we could see coming out of the company when we get the data update in the second half? Would you be willing to share if you would be advancing potentially 2 assets if you had good data? Or is a view that there is going to be one asset coming out of that pipeline review. Any color there on how you're thinking about what the outcome could be of that update in the second half?

Yes. Before I leave it to Mohammed, I'll just say this is a typical Phase 1 exploration, Phase Ib that we are doing, especially when you know that the target is validated. And I think to just address a lot of questions in the early phase before engaging in a late phase, at least when it comes outside of melanoma. But Mohammed, do you want to comment.

Sure. Thanks, Greg, for the question. Look, I think we're in a unique position where we've been in the clinic with brene for several years, and we've now enrolled several hundred patients. So we're certainly mining that data, which will help guide next steps for the brene program. But in addition, as Bahija mentioned , we have the [ PRAME HLE ] trial that's ongoing. And so we're going to be in a good position by the end of the year to look at the totality of the data to guide us with regards to next steps. It just provides us optionality basically.

Our next question comes from the line of Rajan Sharma with Goldman Sachs.

Just 1 on the HIV program that we're expecting an update for later this year. Could you just maybe frame expectations there in terms of number of patients that we should expect that data set to be in? And maybe if you could just talk to how high you think you can push the dose there.

Yes. Mohammed, do you want to take that?

Thanks, Rajan, for the question. Just as a reminder, obviously, the HIV trial is in a multiple ascending dose portion. We shared data last year that showed early dose-dependent effects. So we're continuing to escalate. It's still a Phase I dose escalation. So cohorts are small sizes, but we anticipate by the end of this year to be able to identify the right dose and look at the impact on the viral reservoir as well as the viral rebound.

The other part of the study is that we can trigger expansion based on the data that we see. And so that can allow us to build on any signals we see during those deletions.

Our next question comes from the line of [indiscernible] Khurshid with Jefferies.

I just want to ask how are you thinking about the upcoming competitor readout in frontline uveal from IDEA. I understand it's HLA negative, but do you think there could be any read-through or any impact to your stronghold in frontline HLE-positive uveal?

Ralph, do you want to take it?

Sure. Thank you for the question. So look, we need to see some randomized Phase III data from the competitor. Currently, we've seen only 42 patients with 11 of those patients being HLA-0201 positive. What I'll be personally looking for, in addition to response rate, of course, is the hazard ratio because standard of care has evolved since the beginning of that trial and the safety because small molecules can have tolerability challenges. We've seen another indication. So those are the 2 that I'll be looking for in the data readout.

And we are very much confident that KIMMTRAK is standards of care with very robust data from not only from the clinical trials, but also from the real-world evidence and will bring a 5-year evidence basically that's extending life of patients. .

Our next question comes from the line of James Shin with Deutsche Bank.

One for Mohammed. I want to follow up on the TEBE-AM question on geographic breakdown. Can you lay out the percentage mix in the control arm as in what percent maybe on TILs versus recycled PD-1s and whether that mix may impact historic OS levels.

Thanks, James, for the question. So no, it's a really important question. It's one that we've obviously been thinking about throughout the context of the study. What I can tell you is that we've looked at recent real-world data. And that confirms our original assumptions that about 1/3 of the patients likely in the control and will get retreated with checkpoint.

Those that are BRAF-mutant, typically, get retreated with a BRAF-based regimen. And then the remaining are treated with chemotherapy or clinical trial, reflecting the high unmet need and the lack of an accepted standard. In terms of TIL, your question, as I mentioned in my original response, to Michael, majority of the patients are being enrolled in Europe where TILs are not approved. And so I think we remain confident in the original assumptions of our trial regards to control.

Our next question comes from the line of Paul Jeng with Guggenheim Securities.

I wanted to ask about the second-line cutaneous melanoma opportunity for KIMMTRAK and how you view the evolving landscape, maybe 2 to 3 years down the road where there could be some other therapies on the market, including for the HLA-positive segment. Where do you sort of see KIMMTRAK fitting into that paradigm in the future? Are there any factors like patient baseline characteristics or sites of care that could drive more utilization for KIMMTRAK versus some of those competing therapies.

Well, I can start, of course, Mohammed, you can add to this. So currently, the only approved therapy in the monotherapy of treatment is TILs. And of course, that is highly selective of patients because of the entire process that patients have to undergo through.

Similarly, you mentioned the HLA2-positive TCRT. That is also a highly selective patient population. And of course, KIMMTRAK is -- has -- will have an OS endpoint, right?

Keep in mind, TILs and the TCRT will have response rate potentially PFS end points, we'll have an overall survival endpoint, which is the golden standard in that indication. And importantly, we're off the shelf. We'll have also long-term safety, safety already in melanoma patients of obviously, uveal melanoma. And importantly, we have a great base of experience. We have half of the cutaneous melanoma patients are being treated in centers that are experienced with KIMMTRAK. So all of this together, I think, gives us a significant leg up in this setting. Anything to add?

Yes. The only other thing I would add is that, ultimately, it's good for patients who -- in a setting where there's no high unmet need and no options. It's good for patients to have options. Ultimately, I think what drives the physician choice is based on the data.

And so as Ralph mentioned, our trial is a randomized Phase III trial looking at OS, which is the gold standard. And so I think the data will drive ultimate practice.

Our next question comes from the line of Eva Fortea with Wells Fargo.

Congrats on the progress. A quick one from us, just on Brene. What do you need to see in the coming ovarian and lung readouts to move forward in development? Are you looking for anything specific in terms of efficacy?

Thanks, Eva, for the question. So we -- as I mentioned earlier we've been in the clinic for now a number of years and treated several hundred patients. We already have seen a clear signal of activity in ovarian. We shared that data in '24 at ESMO. But there obviously wasn't a clear line of sight for monotherapy accelerated approval. So we pivoted to earlier lines, the maintenance setting, which we believe plays to the strength of the platform, which is disease control and a very favorable safety profile.

So the data that we're planning to share will be predominantly safety cohorts so smaller than the monotherapy data we shared earlier, but focused on safety and potentially early signals in this maintenance setting, lung we're still signal searching. This is a heterogeneous population. And so the data that we're planning to share will include a data set that's similar to what we've shared with ovarian and melanoma, but it's across multiple heterogeneous subsets. And then, of course, we have safety cohorts looking at chemo combo and [indiscernible] .

Ultimately, Eva, what I would say is that it's going to be the totality of the data. And then in addition, we have the PRAME HLE. So we'll look at the total data to help guide our next steps. .

Our next question comes from the line of Romy O'Connor with Lanschot Kempen.

Just backing on to eva's here, focusing on the half-life extended PRAME. I just want to ask if you can point us to what we need to see here to inform any major changes to the PRAME program in totality. You mentioned convenience and improved response. Should we be benchmarking this against what brenetafusp already shown?

Great question. Mohammed?

Thanks, Romy, for the question. Yes. No, exactly. I mean as we said, we're in a very good position where we have our brenetafusp data and essentially PRAME HLE is brene with the Fc added on. And so we're doing the right experiment in the clinic asking those 2 basic questions. And based on the data, it will provide us optionality in terms of which molecule to carry forward in which setting..

Yes. I think the when we started is really look at convenience because we see with KIMMTRAK with short half-life an amazing hazard ratio of 0.51. Now I think with the other data out there, if we see also an increase in ORR or something like that, then I think that's what mohammed was talking about is looking at the totality of the data, and then we'll determine the next steps. But we are very -- we'll do the experiments, and we'll get the data. .

Our next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Just a couple of follow-ups on TEBE-AM. I'm just wondering, given the OX primary endpoint, what was the assumed median OS in the control arm? And has anything in the real-world evolution of the treatment landscape changed that assumption since trial initiation. And then just separately, just regarding the timing of the data as early as second half '26. Maybe you can give us an idea of what the event assumptions are driving that and the probability that the data perhaps looks into 2027.

Okay. I'll take the second part, and then mohammed will take the first part. So because it is an OS endpoint, it is event driven. So we'll have a little bit better idea maybe when the trial is done, but it's going to depend on the event. That's why just doing the calculation that we did and the assumptions that will basically we see it today as early as the second half of 2026. So we'll get a little bit better once we finish the trial and depending on the events. But mohammed, do you want to take the first part?

Sure. Thanks for the question, Patrick. So with regards to OS assumptions for the control arm in TEBE, the assumptions we made at the start of the trial really haven't changed because ultimately, there has been no randomized trial that's actually established in improvement in survival in this setting. So those assumptions essentially were a median overall survival between 12 and 13 months and a 1-year survival rate of around 55%. Things haven't really moved from that regard. .

Thank you. We have reached the end of our question-and-answer session. And with that, I would like to turn the floor back over to Morgan Morris for any closing comments.

Thank you for joining us today. We appreciate all of your support.

Thank you. .

Thank you, ladies and gentlemen. This does now conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.

Great. Good morning, everyone. My name is Jess Fye. I'm a biotech analyst at JPMorgan, and we're continuing the 44th Annual Healthcare Conference today with Immunocore. First, you're going to hear a presentation from the company, and then we're going to go into a Q&A session. [Operator Instructions].

So with that out of the way, let me turn it over to Immunocore's CEO, Bahija Jallal.

Good morning, and thank you, Jess, for having us. It's always a pleasure. This is our forward-looking statement. Our mission at Immunocore is to bring transformative medicines to patients. We are a commercial stage biotechnology company that pioneered the first soluble TCR receptor bispecific platform. This platform is validated clinically and commercially.

And what's really interesting about this platform is very modular. So it can upregulate the immune system by redirecting the T cells to kill tumor cells and infected cells, and that's useful, obviously, in oncology and infectious disease or it can down modulate the immune system in autoimmune diseases. 2025 was a year of execution for Immunocore. '26, '27, '28 is really where things will come together as we're going to have several data catalysts.

But let me focus on 2026 today. Our priorities are very clear in the company. One is to grow KIMMTRAK and prepare for potential new melanoma indications. The second is to expand beyond melanoma into other tumor types. And third is to unlock the value of the opportunities beyond oncology. I will walk you through all the 3. So let's start with the first one. KIMMTRAK was approved 5 years ago as the first treatment for metastatic uveal melanoma in 40 years. And this was done with a landmark or a gold standard of overall survival. was absolutely necessary for these patients. But the question is, how did it do really in the real world?

And here, we have the data to really see that actually in the real world did even better. So we have the duration of treatment, the main duration of treatment is 14 months. It surpassed what we've seen in clinical trials. We published the 3-year survival data. It was also a very, very important data. But the latest data that we just said or/and the latest data that we've just said in -- we showed in ESMO I-O showed in a real world, now taking a registry from France with 150 patients, a median OS of 28 months.

And we can see that translating into the commercial arena. We have 70% penetration in all the major markets. We have some markets where we have 90% penetration, 80% penetration and so on. So that tells you that there is a really need for this drug, and it's working. And of course, it translates into the commercial arena where we have 30% growth -- revenue growth. This year, we have -- since we launched 14 consecutive quarters of growth. So what's next for KIMMTRAK?

We will be publishing this year in the first half of the year, the 5-year OS data. And we believe the biggest potential opportunities for KIMMTRAK is yet to come and still ahead. So how are we looking at in 2026. One is to continue the U.S. penetration into the U.S. market. and the global expansion in mUM. So basically reaching -- it will come, my coffee is not kicking in. So the expansion is into more and accessing more patients around the world. The second is, the expansion into second-line cutaneous melanoma now. We're starting to look at the life cycle management with 2 Phase III trials.

The first one is the TEBE-AM, and I'll talk to you about it. And the second is the adjuvant uveal melanoma. So let's look at the cutaneous melanoma. We know that the market opportunity is around 4,000 patients, HLA-A2 positives. And there is a unmet medical need for population beyond PD-1, basically resistance or refractory to PD-1. What's the reason to believe we had the trial, the Phase Ib trial with 60 patients that showed that for this population, 1-year OS was 75% compared to 1 year OS of 55% for the benchmark. So we started the Phase III trial in second-line plus cutaneous melanoma. And the design is the following.

We had KIMMTRAK. KIMMTRAK plus anti-PD-1 or straight to follow-up or, if you will, the investigator's choice. The endpoint is the overall survival. So where are we with this trial? This is the next milestone for us. We are on track to finish the enrollment of this trial in the first half of 2026 with data that could be as early as the second half of 2026. Now looking at the adjuvant uveal melanoma. So what happens after the first -- after the primary tumor is the final treatment, if you will, for the primary tumors, the patients with metastatic uveal melanoma with 50% of them will develop will develop metastases in the next basically 3 years. There is nothing for these patients right now, except for basically what we call the watch and worry.

So it's just surveillance. And our value proposition with KIMMTRAK is to bring and impact the disease at earlier point, hopefully delaying or eliminating even metastatic -- the metastatic score for these patients. So this trial is ongoing. If you look at the market opportunity is 1,200 patients. It's ongoing right now in collaboration with EORTC. We are enrolling patients in Europe very actively, and we'll start enrolling patients in the U.S. as well. So you can see with this life cycle management, we can go from 1,000 patients in metastatic setting today that we are serving today up to 6,000 patients with the 2 trials that I just talked to you about. And we don't stop there for melanoma. We have another in cutaneous melanoma. We have another shot on goal, as we call it, and that's with Crane.

So first, let me introduce PRAME to you, it's a great target for different reasons. The one is highly expressed in cutaneous melanoma. It's also a negative prognostic marker. So that means the tumor is not like to lose it. Its target is clinically validated across multiple modalities by us and others. And we have demonstrated monotherapy activity and that it combines very well with checkpoint inhibitors. So we've shown, as I told you, we shown that there is a monotherapy that is active in cutaneous melanoma.

And we started the Phase III trial. This is PRISM-MEL, a Phase III trial in cutaneous melanoma, but now we are going into first line. So we have KIMMTRAK in the late lines and PRAME in first line. So there were 2 milestones for this trial. One was the safety run-in, if you will, which was very successful. The second one was -- for this trial was part of the project Optimus for the FDA. So that means we had 2 doses going into the trial and the independent data monitoring committee was to look at which dose to take forward and which one will drop.

We achieved all that in November in 2025 and the IDMC chose the highest dose. And so this trial right now is continuing without with dropping 11 dose. It's all over the globe. So we have 200 sites open. It's enrolling fairly nicely. And if we continue on that trajectory, we anticipate to finish enrollment by 2027. The market opportunity here is 10,000 patients that are HLA-A2 positive. So as you can see in melanoma, we have multiple shots on goal, and we have -- but we can go even beyond melanoma. So that's the second focus right now is, again, looking at PRAME. So PRAME is Interesting, I told you a target not only because it's expressed in melanoma, but it is expressed outside melanoma in ovarian and non-small cell lung cancer among other tumors as well. So we already showed monotherapy activity in ovarian, and we show that it combines very well with chemotherapy. We present this data at different times, either in melanoma or ovarian.

But what was really important for us now is we know that in that is to explore even more in ovarian, not only in platinum resistance, ovarian cancer, also in platinum sensitive ovarian cancer, either as monotherapy or in combination and move even earlier. We are doing the same thing in non-small cell lung cancer. So that we have basically the signal searching in non-small cell cancer. So this data will be -- is being generated and will be developed into this year. I will tell you that by the second half of 2026, we'll be presenting this data.

But what's also really exciting is we have the PRAME half-life extension that's in the clinic. We put it in the clinic at the end of last year. So in 2025 -- in 2026, we'll continue the dose escalation. So we hope that by the second half of 2026, and we plan for the second half of 2026, we'll have data for all these 3 experiments, if you will, that will allow us to basically plan what's next step and which molecule to take forward. And last but not least is PIWIL. So PIWIL is a novel target that was basically discovered by us. We have -- it's also a really important target because it's expressed very widely in 25% of colon cancer.

Basically, 75% of tumor cells are positive for PIWIL. It's expressed in other GI cancers like pancreas and others, but we're very much focused right now on colon cancer because of the unmet medical need. So we have 20,000 colorectal and 15,000 other tumor patients that are positive for PIWIL. But you know that there is a huge unmet medical need right now and especially where checkpoint inhibitors have not worked as well is in colorectal cancer. So where we are with this program, we get it -- and we started the end of '24, literally in December. So we are in dose escalation, it's going very well, and we hope to have data either this yeasr or 2027.

But this platform, like I told you, is modular. So we can go -- we have opportunities beyond oncology. First one is in HIV. So we know that HIV is very well served with antiretroviral. What we are really looking for is a functional cure and going where nobody has gone there before. Because you know antiretroviral do very, very well. However, when you stop, you have to take them all the time. When you stop, you can see less than 2 weeks, you can start having the viral bound. And if you look at over 500,000 patients HLA-A2 positive today of people living with HIV are currently on entire retroviral.

So we showed the single ascending dose with our [indiscernible] the first compound in -- for HIV. And what we're trying to do is really the -- you see the rebound because there is -- basically the virus heights in a reservoir. And so our value proposition is to go and actually attack that reservoir and then see if we can actually basically have an antiviral effect or -- so what we've done, the single ascending dose show that it's safe and we can continue into the multiple ascending dose. At the beginning of 2025 [indiscernible], we showed the first data of our multiple ascending dose. And there are really 2 things.

It was very well received by the KOLs, I have to say. And we have 2 important points: one is that it's very well tolerated; and the second is we are -- it is -- we saw dose depend antiviral effects. If you look at the blue lines, 60 microgram, which is the lowest dose, you can see when you stop everything, our compound plus the antiviral, everybody takes off. And then you can see in the orange as you get 120 and 300 micrograms, you have delay the viral rebound. That's what we're really looking for.

We don't believe that we are at the most effective dose yet. So we are continuing the dose escalation into much higher doses and we hope to get this data at the end of 2026, the second half of 2026. What's really close to my heart, and I think absolutely exciting in autoimmune diseases. I think it's an area where we need more -- absolutely need more innovation. And instead of really looking for systemic immune suppression is what we're trying to do is to go very much organ-specific down modulation of the immune system, right?

So we do it because in our -- we can have the tissue tethered molecule, the TCR. And on the other side, the first one, starting with is the agonist, is PD-1 agonist. So we chose to go into type 1 diabetes because we have -- there is -- first an unmet medical need. You still have 50,000 patients that are newly diagnosed with type 1 diabetes every year.

And we made basically a construct that binds to the pre-proinsulin on the beta cells that are specific just the pre-proinsulin is expressed only in beta cells. So we're bringing our molecules to bind to the pre insulin, and on the other side, basically switch off the autoreactive T cells with PD-1 agonist. Very, very quickly on this one. We just to show you how specific it is. These are pancreatic slices from human beings, if you will. So you can see the beta cell marker, and you see that when we put our construct is specifically binding to the beta cells. But not only that, on the -- on my right, you can see that not only we bind, but we also rescue the beta cells from killing. And then the question is, if you rescue from killing, is it functional? I'm not showing the data here, but it is functional.

It's the secrete insulin. So we have a real rich data package preclinically that convinced us to move into the clinic. We filed the CTA in December. And I think we have really a very good experiments that can be done that we can find out early in the clinic Phase I and Phase Ib basically if it's working or not, which I think is very, very exciting. And then you can imagine if this works, that opens up any T cell-driven diseases that we can go after. And not only that, we can go even beyond with autoimmune.

So with that, I'm just going to show you -- I told you to really focusing on 2026. It's going to be a very busy year. The first half is very much on continuing to enroll the TEBE-AM and finish that enrollment. And then we are in the autoimmune diseases in type 1 diabetes to start the trial. The second half is much busier, and we hope that we'll have data there for TEBE-AM. And then you can see, as I walked you through some of the data readouts that we have with the PRAME and other things. But it doesn't really stop in 2026. As I told you, we're now looking forward to '26, '27 and '28, where we're going to have data catalysts coming after the labor of the last 3 years of enrolling, especially Phase III trials and so on.

So I'm going to leave you with the 3 key takeaways. We have validated product in the real world in commercial, but not only that, we have actually a 30% increase in revenue and 14 consecutive quarters of growth that really sustain it actually speaks very highly of the drug, the KIMMTRAK. We have 3 Phase III trials in melanoma that are ongoing with data readouts starting in 2026. And then we have a diversified pipeline, as I showed you, one that we believe is, we have shown proof of principle in infectious disease but can be the unlocking the value in autoimmune disease is the next step for us. So with that, I just want to thank you and thank all the teams in Immunocore, and we'll call my team to come answer all the tough questions.

Great. Thank you. So it looks like there's a lot going on with the pipeline this year, but I did want to start out with KIMMTRAK. If we turn the page and under 2026, what are the key growth drivers from here? .

Yes. I think I'm happy to start with that. Jess, thank you for having us, by the way. So if you look at KIMMTRAK in the current uveal melanoma indication, as Bahija highlighted, we are greater than 70 penetrated in all major markets and even 80% and 90% penetrated in some European markets. That strong penetration has allowed us to grow in the first quarter of 2025, 30% year-on-year. So as we move into 2026, what we'll -- what we do anticipate, this is our fifth year on the market. So naturally, we do anticipate some growth to moderate, but we expect that growth to come from increasing the penetration in the U.S. community setting and as well as further goal expansion outside the U.S. Beyond -- that's for the uveal -- current uveal melanoma indication. Beyond that indication, we have 2 life cycle Phase III trials ongoing.

One is TEBE-AM, the advanced cutaneous melanoma indication was Bahija highlighted, we anticipate completing enrollment in the first half of this year with data as early as the end of the year. That second -- that life cycle management indication has the potential to increase our current eligible patient population from about 1,000 patients to an additional 4,000 patients. So it's a significant inflection point particularly for us. And then the second life cycle management indication is the ADAM study, the uveal adjuvant uveal melanoma trial. That trial is ongoing. We just started that late last year, and it's enrolling well. And that has the potential to add an additional 1,000 patients. So if you look across the horizon of the current uveal melanoma indication that we have alongside the 2 life cycle management indications, that could take our eligible patient population from 1,000 to up to approximately 6,000 patients over time.

So recognizing that kind of the next big tebe readout is in cutaneous and not uveal, if that hits, does that create like an additional halo around the product that could help deepen your penetration in uveal?

I think if you look at where we're at, we have 2 objectives with increase in the U.S. community penetration. One is increasing the patient starts. And the second is, and it's tied to the first, is bringing that treatment closer to patients' homes. We've been -- we've made good strides in that already in that, we have about 50% of our patient starts coming from the U.S. community currently and about 70% of the prescriptions. And what has allowed us to do that is the drug's profile.

Patients are living longer. We can hear from patients all the time, they not only live longer, but they feel better. And that is -- obviously, that's driven by efficacy, but it's also driven by the safety profile that we have. It's predictable, it's manageable. And that is a testament again to that drug's profile, which has allowed us the success in pushing into the community that we've seen thus far today. I think all of that translates into the cutaneous melanoma indication as well.

So Jess, I think just to add. So when we look at markets like France, we are 90% penetrated already. Germany, 80%. I think we still have some room to go in the U.S., that's 70%. But I think the other -- for cutaneous melanoma to your point, we're not going to be starting from scratch because 50% of the patients who are treated for cutaneous melanoma are treated in centers that are familiar with KIMMTRAK. So just to add to that.

And is it a structural phenomenon that kind of accounts for why the U.S. penetration is a little bit lower than some of those European Countries?

Yes. Yes, community centers, if you think about Europe, you're very centralized payer systems, right, reimbursement systems. U.S. is very dispersed. So there's very low density of patient populations in that dispersion. And so what we do is to help achieve those objectives that I mentioned earlier is we use advanced analytics and AI because we have a very fit-for-purpose footprint given a relatively small indication that we have today. So we leverage the advanced analytics to help achieve the objective in that penetration in the U.S.

For the ADAM adjuvant trial, where do you stand with kind of progress on site activations? And what's the best thinking on timing for that data?

So the EORTC is running that trial, and they have it activated in Europe, and we should have sites activated in the U.S. now. I think this year is the year will probably reach steady state accrual. And right now, we've penciled in a 3-year time line for randomization, started in the fourth quarter of '24. So I would imagine by the end of '27, we can finish accrual or early '28. And then it's event-driven. So it's probably 18 months or so after that would be the analysis -- would be the events. But it's certainly too soon to have a fine-tuned projection of events better certainty on the enrollment.

Okay. And maybe shifting to brenetafusb from the PRAME asset. After selection of the high dose to continue in the Phase III trial, have you been able to refine your projections for enrollment completion and top line data?

Yes. So we are now down to 2 doses, which is good. It helps the trial accrue. We have, as Bahija mentioned, over 200 sites globally enrolling, and it's enrolling pretty well, actually. So right now, what we're projecting is to complete randomization at the end of 2027, it could bleed into '28 that we're trying to push for 2027. And then, of course, it's event-driven after that. And typically, in these first-line Phase III trials, PFS usually reads out not that long after all the patients have been randomized. But it's -- in terms of event prediction, I think we'll have a better sense next year.

What specifically gives you confidence in Phase III success with this asset?

I think there were multiple factors that led us. First, when we enrolled brenetafusp monotherapy in late line, we saw some durable partial responses. So we know the drug is active. But we also saw pretty high disease control, which was this closed umbrella type plot. In fact, the disease control rate for brenetafusp monotherapy was higher than the disease control rate for the combination of nivolumab plus relatlimab or LAG-3 in the same population that was [ relTivityY ] study 20. So a monotherapy brene had more activity than the combination of the both.

The second piece was we've done some -- a lot of work into understanding T cell fitness in blood, and we found that T cell fitness improves in -- as you move into earlier lines and the activity goes up with better T cell fitness. So we projected that there would be higher activity in earlier lines, including first line. And this is not unusual in immunotherapy. And then the final point was we knew that when we -- if nivo plus LAG-3 beat nivo in first line, we felt that adding nivo plus brene, so 2 active agents, each with a different mechanism of action would be better than nivolumab, and also would be better than nivo plus LAG-3 because of the monotherapy data. So those were the data points that led us to launch the Phase III trial.

I will just add. So I think looking at the mechanism of action and to active will have at least an additive effect, we'll see the trial will tell us if there is synergetic effect as well because they're 2 different MOAs.

So it sounds like we're also getting more data in other indications outside of melanoma for branding coming up. So as the ovarian and lung data continue to emerge, how could DCR and kind of response durability influence future pivotal planning in those indications?

I look at ovarian and lung in 2 different ways. For ovarian, we saw monotherapy activity for brenetafusp in late -- in late line ovarian, although it wasn't enough to advance, given the rapidly changing landscape. But we know the drug is active. And so knowing about the mechanism, we realized that we should try to move earlier, which -- hence, the platinum-sensitive cohort with bevacizumab. First time ever a T cell engager with bev is being tested. And then we also wanted to expand on the chemotherapy combination in platinum-resistant. In both of those cases, now, we're going to look at the data later this year, and the strength of that data will determine what the next step is.

We'll be looking at, is there further reduction when you add [indiscernible] on top of bevacizumab because this is a maintenance setting. And with chemotherapy, is there a higher response and a more durable response with -- in that combination. And the strength of that data will determine what the next step is. It's likely a randomized trial, but it will determine, but the strength of data determines is it a randomized Phase II? Is it a Phase II/III or is it a Phase III? And we also have the PRAME half-life extension, which is moving in parallel, and we can talk more about that. For the lung, it's more of a signal detection because lung in this late line is a very difficult tumor.

Just to kind of keep picking it long there though, if you do see the signal that you're hoping for, then what is the next kind of development step look like?

So depending on the strength of the data, I think we would choose to partner, the combination partner, where we saw the strongest signal, and we would probably do a randomized trial because in this case, we're adding 2 active agents together. And although you like -- you can see signals above a background of one of the agents, you never know until you run a randomized trial. So we would likely need to run a random trial.

Okay. And when you say combo partner, you mean combo drug bio company.

Yes.

Yes. [indiscernible] partner.

Biotech company.

Yes. Yes. Sorry, correct.

Is it a chemo or is it the bev for...

Osimertinib chemotherapy anti PD-1. Yes.

Okay. Great. So what's the next update we should expect for the half-life extended PRAME product? And how do you think about the next development plans for that asset? Like what data that you generate with Bi kind of factor into how you advance that product?

Yes. So that's why we're lumping it, if you will, with the totality of the data because one thing for the -- half-life extended is the molecule is almost the same except for the FCE. So we believe whatever we see with brene is going to be relevant if we choose to continue with the half-life extension.

So for the high life extension, we are really 2 things: one is it for convenience, right? So that's our first hypothesis; and then the second, does it increase the ORR and other things will we know, but we can swap that. I do believe that we can have used the data from brene if we want to continue with the half-life extension. So we'll have the data first. I think most of the -- even the dose escalation, we have cutaneous melanoma ovarian, things where we have already data with brene.

And what's the difference in dosing frequency between the 2?

So the traditional is every week. And then with the half-life, it's actually flexible. It could be every 2 weeks, 3 weeks.

So thinking ahead to the potential Phase III melanoma readout for brene. What kind of regulatory interactions could streamline a potential approval there in melanoma? .

Yes. We all take really advantage of whatever pathway we have with the FDA. So there are several points where you can actually interact with the FDA. One is on the statistical analysis plan. You can do that on the narratives on the clinical side, you also can -- once you finish the PPQ batches on CMC, you can interact with them. So all these can be done before you actually have the data. And we find we found that out to be very, very useful, actually getting the guidance from them, and we're very grateful that they give that guidance before.

So you're not the only company who thinks PRAME is an interesting target. So what other products are you watching competitively? And how is Benny kind of differentiated from them? .

Yes. No, definitely. I think the data from Immatic looks really very promising. It's always good to see different modalities on target, basically that just brings you even higher confidence in the target, right? So basically, what we've seen either with TCR-T for what they produce or the bispecific that PRAME is definitely a good target as we started a few years before. I think it's the early data. So I think it's very, very promising.

So maybe shifting to the pipeline. You mentioned you're particularly excited about the efforts for type 1. As that moves into the clinic here, what marker you look at in Phase I to help assess the tissue-specific immune modulation?

Yes. So we chose that -- the type 1 diabetes because you can actually -- you don't have to go all the way to big Phase IIb to find out if it works or not, like we're not that kind of company. I think we have with the single ascending dose and the multiple ascending dose, we can address 2 questions. And the first one. The first basic one does the drug hit the target, basically?

And that I think we have -- we can do a lot of exploratory things, but one very solid biomarker, there is the solid PD-1. We know that there is a soluble PD-1. If it increases, then you know that it binds to that. On the multiple ascending dose, we can actually start addressing at least a biomarker of activity, if you will. So if everything is working as we believe, then you can do the C-peptide levels basically after the mixed meal test, if you will. And we know that the FDA is even considering or at least Sanofi is trying to have the C-peptide as a marker. But you can...

Yes. I just want to add one other set of assays that we're looking at, which are immunologic autoimmunity. So first of all, auto antibodies, which are known to be reflective of disease activity, we would look for those to go down potentially in the SAD. And then the second is our scientists have developed assays to measure autoreactive T cells and the exhaustion, whether they're exhausted or not, which is the exact mechanism of action that we're looking at. So we can follow those autoreactive T cells. The T cells that kill the beta cells. We can follow them over time, and we would expect based on the mechanism for those to become exhausted, and we could potentially see that in the SAD, which we think will complete this year.

Does that mean we see the data this year?

Probably next year, I would say, '27.

Beginning of '27.

Yes.

Okay. And I guess what's the ultimate kind of target product profile here? Let's say, you see something on C-peptide. Is there a certain kind of threshold that tells you like to full steam head versus we need different dose, kind of more work.

Yes, you can go.

Yes. So C-peptide, preventing progression of type 1 diabetes is still in the early stages. There's only one trial, really, the Sanofi trial that had reduction of C-peptide. And we'll see whether that is going to be the regulatory end point. Our target profile is going to be patients who are newly diagnosed with type 1 diabetes.

So they still have a beta cell mass to protect by the -- in late-stage T1D, there's no more beta cells left, is to protect those beta cells to give a finite dosing regimen so that we can induce exhaustion in the autoreactive T cells. And after that finite dosing regimen, we hope to have a disease-modifying effects so that the patients can stop treatment and potentially beta cell regrowth can occur or at least no more decrease. So C-peptide is a marker of beta cell selectivity. You also look at use of insulin, hypoglycemic incidents. And so there are other endpoints, but we are trying to have a disease-modifying effect with a finite duration of treatment.

So you also talked about the pivotal directed asset. So following escalation, what do you want to see for safety, PK, what's going to inform your decision about advancing that further? .

It's really we're looking at activity. We know enough of the platform now that the safety is not an issue, right? That also the PK is not an issue because we see the OS has a rate of 0.51 with TEBE that has a very short half life. So we'll be looking at the characteristics that we see in our platform. Do we have durability, the DCR, the ORR everything. And we know if it hits the target, we look at cytokines and things like that, but we'll be looking at activity basically.

And just to add one thing, even if PIWIL is a KIMMTRAK like drug with a low response rate and very good survival, it has a direct path forward in late-line colorectal where the current survival is very dismal and the response rates for therapies, there are less than 10%. So much interest in PIWIL, and we'll complete dose escalation this year with the data next year.

Question on that. We're out of time.

[indiscernible] Obviously, [indiscernible] now going more [indiscernible] expected [indiscernible] that you've also got a lot going on the clinic. I mean, roughly, what are your funding requirements [indiscernible] in next couple of days? [indiscernible] funding.

Yes. Actually, pleased. We -- so year-on-year, we actually increased our cash. We ended the year with unaudited, but about $860 million of cash on the balance sheet. At this time last year, we were about $820 million. So we continue to -- I think the more important thing is the capital allocation strategy. We're investing in the Phase III, Phase III studies. We're continuing to advance the portfolio. And we're doing so from an R&D expense investment perspective. We're doing so in a data-driven manner with our R&D expenses, and we're staying very disciplined with our SG&A expenses. And that's the philosophy that we have with respect to the capital allocation.

Great. We're out of time, so we'll stop there. Thank you.

Thank you.

Thank you very much.

Thanks, Jess.

Thank you.