Great. Welcome. Good morning, everyone. My name's Jess Fye. I'm a Biotech Analyst at J.P. Morgan, and we're continuing the 43rd Annual Healthcare Conference this morning with Immunocore. First, you're going to hear a presentation from the company's CEO, and then we're going to go into some Q&A. If you've got a question in the room, raise your hands and we'll bring you a microphone, or you can send questions via the portal up to me on stage, and I'll ask them from the iPad. So with that, let me turn it over to Immunocore CEO, Bahija Jallal.
Good morning, and thank you very much, Jess. It's always a pleasure to be here. This is our forward-looking statement. For some of you who are new to the story, Immunocore is a commercial-stage biotech company that pioneered the first T-cell receptor engager. We have a very robust late-stage pipeline with three phase IIIs that are ongoing. Very rich early pipeline that spans three therapeutic areas: Oncology, Infectious Disease, and Autoimmune Diseases. All that supported by a strong and robust revenue from our first product, KIMMTRAK. We made the commitment to bringing transformative medicines to patients. We realized the first steps of that mission with the approval of the very first and only T-cell receptor in solid tumors, namely KIMMTRAK in uveal melanoma. And it was transformative. The endpoint was an overall survival with a hazard ratio of 0.51.
But what has more impact, in my view, is when we actually have the privilege of talking to patients. Patients who, before KIMMTRAK, were given 12 months to live. On KIMMTRAK, they are two years, three years, four years later, they're thriving. This is why we come to work every day. And then the question is, can we do it again and again? And I hope I'll convince you that yes, this is exactly what we're doing. And the reason being that we built a very strong foundation. A foundation built first on cutting-edge science and a technology or a platform that actually we can continue to build upon. The second is we have the world's largest database that... Okay, now we have it again. All right.
We have the world's largest TCR clinical database that allows us, and also insights from research that allow us really to use our capabilities in translational medicines to bring the insight back and forth from the clinic to research and research to the clinic. And an experienced leadership team that's associated with 30 compounds that are on the market today. That's what led to this very deep pipeline, but also diversified pipeline. And our strategy is very simple and based on three pillars. I'm going to walk you through these pillars, but most importantly, I'm going to actually tell you what we have accomplished in 2024 and our outlook into 2025 in the next 12 - 18 months. So the first pillar is maximizing the potential of KIMMTRAK. The second is advancing our rich clinical portfolio.
Lastly, the innovation, basically how we bring more from research and continue to innovate and feed into the pipeline. Let's look at KIMMTRAK first. KIMMTRAK, like I said, is our flagship compound. It's the first one we have in oncology. We launched in 23 countries. Just in 2024, we launched in 13 countries in 2024 alone. We are approved in 38, so we will continue to bring KIMMTRAK to patients who need it around the world. And thanks to really an excellent execution from the commercial team, we have had since launch 10 quarters of growth. Just in 2024 alone, going Q1 to Q3, we had $226 million. We will give the final number for 2024 in our Q4 results in a month or so. We see more growth in KIMMTRAK due to two things.
We are only 65% or we are 65% penetrated in the U.S., so we have still more to go, and especially now in the community. And the second is the duration of treatment. It's been really amazing to see the duration of treatment not only match what we've seen in clinical trial, but increasing still. And we will continue the launches as I talked about. So we see more growth, and we will be reporting on that, obviously, every single quarter in 2025. This is in the short term, and this is what we have with KIMMTRAK in the short term. When we look at the life cycle management, we have the first phase III that's ongoing, and that's basically in the second-line melanoma, cutaneous melanoma. There is an unmet need, if you will. This is second-line post-PD-1.
Right now, only TILs are approved as accelerated approval, and we're coming with a randomized trial with overall survival as an endpoint. This trial is ongoing. We have the line of sight on when we get the data. We have basically the trial will finish enrolling, hopefully, in Q1 2026 with the data in the second half, in the first half of 2026, with data in the second half of 2026. If we are successful, that adds 4,000 patients that are eligible for KIMMTRAK.
The second trial that I'm really excited about as well is the adjuvant trial. We call it the ATOM trial. The unmet need there is absolutely visible because when you have uveal melanoma that occurs in the eye, what happens is that once you have the final treatment, if you will, which is sometimes removal of the eye, you have to wait.
We know that 50% of patients will relapse or have metastasized to the liver. During that time, there is nothing. It's about watch and worry, as we call it. Basically, it's observation for these patients until they progress, so what we are proposing with this trial that's in collaboration with EORTC is actually to treat during that time and hopefully either delay or completely eliminate those metastases from patients, so if we are successful, the trial is ongoing. I think in 2024, as we promised, the first patient was enrolled already, so it's ongoing right now, and if we are successful, that adds another 1,200 patients to KIMMTRAK eligible, so taken together, what you see today in the short term, today we have 1,000 patients that are between the U.S. and major countries in Europe that are eligible for KIMMTRAK.
If we are successful with life cycle management that we are doing in the two phase IIIs, we can go up to 6,000 patients that could be eligible for KIMMTRAK, which expands then the reach of KIMMTRAK and also the revenue. So now moving to the second pillar, which is advancing the clinical portfolio. I'll talk about PRAME. PRAME is an interesting target because it's highly expressed in tumors. It's also a negative prognostic marker.
That means that the tumors don't want to get rid of it, if you will. We have shown that PRAME is active as monotherapy in cutaneous melanoma. We saw a very durable disease control. And when we looked at the, which is one of the hallmarks of our platform, the disease control rate, we saw a very high disease control rate, especially compared to some monotherapies or even combo therapies in this setting.
That basically got us to move PRAME in Cutaneous Melanoma into first line in combination with Nivo. This is our phase III that we call PRISM-MEL. That's ongoing right now and enrolling patients as we speak. Moving from melanoma, we also showed that in ovarian carcinoma where PRAME is expressed, that we have monotherapy activity. And we actually see as well two things. One, that we can combine with chemotherapy very safely. This platform actually can combine with multiple modalities. And then we saw some interesting signal, beginning of signal, I think, in the combination therapy. So the next step, this was all in platinum-resistant ovarian carcinoma. So the next steps, what we are doing right now, is actually shoring up this data to have more expand a little bit more in platinum resistance.
But from the insight we're having for our platform, it's also important to move earlier. So we are also doing the same experiments in platinum-sensitive ovarian cancer and also in combination. So we'll have that set of data in the next 12- 18 months. And then non-small cell lung cancer, where also we know the T-cell therapies are active in non-small cell lung cancer.
There we are looking at signal searching, but also taking the learning of moving earlier and also in combination. So our goal in 2025 is to really have a robust set of data that will allow us to move into the next step or at least make the decision of moving into the next step. So we have a very active target discovery. And the next target that came from our research that's now in the clinic is PIWIL. PIWIL is an interesting target.
It's really an exciting one because it's expressed in colorectal and also in GI cancers. As you know, unfortunately, the CRC, the incidence of colorectal cancer is increasing, and also there is, as you know, the MSI-High and MSS. MSI-High is a small portion, if you will, of colon cancer that's sensitive to immunotherapy. However, the majority of the colon cancer, which is the MSS, is not sensitive to immunotherapy. The good thing about PIWIL is we see it expressed in both, in MSI-High and MSS. So we are in, and it's also a negative prognostic marker. We like those, so where we are in 2024, we filed the CTA. We had the first patient enrolled.
We are in dose escalation, and we hope to bring in the next 12- 18 months, depending on data-driven, first looking at the dose, looking at safety, and of course, any sign of activity. Now moving into our next therapeutic area, which is infectious disease. As you know, the first program we have there is in HIV. We know that thanks to antiretroviral treatments, that HIV is no longer a death sentence. It's a chronic disease now.
And for patients who are or people who are living with HIV, one problem is they're not cured. So if they stop the antiretroviral, we have what we call the viral rebound. The reason being that there is a reservoir where the virus hides. And so our proposition is actually for a functional cure and to go after that reservoir. We have a multiple ascending dose. The single ascending dose we presented already, but this is now the multiple ascending dose where we are asking two important questions, questions that have not been addressed before.
One is, can we reliably eliminate or touch the reservoir? And nobody has been able to do it reliably before. And then the second part of the question or second question is, if we touch the reservoir, would that have an impact on delaying or eliminating the viral rebound when we stop all the treatments? So we are on track. We said we'll be presenting the data at the conference in Q1 2025, so any time soon. And we're on track. And then we'll continue. We actually didn't hit the dose-limiting toxicity, so we're going even higher with the dose, and we hope to bring the full data at a later point.
And then, coming to innovation coming into the pipeline, is actually looking at how modular our technology is. And we believe that we can be also differentiated, and that's in the autoimmune area. This is our third area. The differentiation here is right now, when we look at autoimmune is a chronic disease as well, we see a systemic immune suppression of the immune system. And that has also some side effects that we can discuss. Our approach is to go very much organ-specific down modulation of the immune system. So the way we do it is basically we have a TCR that binds to very specifically to the organ of interest where the inflammation is happening. And on the other side is to bring the PD-1 agonist that basically will switch off or inactivate the autoreactive T- cells.
We add an Fc fusion for convenience and for half-life extension, if you will. So that's basically our differentiation. The first project we're working on is the Type 1 Diabetes. And there, because we have identified the preproinsulin as a peptide that's expressed only in beta cells, so we can tether our construct in the beta cells. We've shown here that you can see in green the beta cell marker. In red is the PPI, our compound basically binding exclusively to the beta cells. And we can show that we can, by doing so, when we have the PD-1 agonism, basically PD-1 in the right place, that we can rescue the beta cells from killing. We have a lot more preclinical data that we will be sharing this year with everyone and hopefully also publish.
But that gave us confidence and the reasons to believe to move into the next stages and to get to the clinic in 2026. So for 2025, we are on track actually to filing a CTA towards the end of the year. We are right now in GLP manufacturing. And the second target that we actually talked about only this year is the CD1a. So CD1a is an HLA-like protein that plays a key role and it's a hallmark of Langerhans cells. So Langerhans cells, what are they? They are basically antigen-presenting cells in the skin and the mucosa. They present lipid and peptide antigens to T- cells. And so they are involved in atopic dermatitis, in psoriasis, allergic asthma, and others. So there was already a compound out there that targeted CD1a, but we believe it's not enough.
So the differentiation, what we're trying to do is to actually block both mechanisms, not only the presentation, the lipid presentations by the CD1a, but also the peptide presentation on Langerhans cells. We're very excited about that. We will be presenting data this year as well on the preclinical, but we moved now. We have clinical candidates and we're moving into GLP manufacturing and getting into the clinic. This will be six months after the Type 1 Diabetes. All in all, I just want to finish. I think I gave you all along what we have a very busy, a very active 12-18 months with data-driven and data-rich 12-18 months.
How we're doing all that is very strong, a very strong balance sheet that this is preliminary, but basically allowing us to focus really on doing the right experiments to bring very transformative medicines to patients. And with that, I just want to thank you.
Great. Thanks for the presentation. So David Berman and Travis Coy, the new CFO, joining us on stage. Maybe just start out. Can we talk about KIMMTRAK and what's going to drive growth in 2025?
So really two things. One is we launched in 13 countries, as you know. So now we are up to 20. And we are approved in 38, so we still have some launches to have. As you know, we had also the U.K. at the end of the year where we agreed on the pricing. So we'll be launching in the U.K. and Poland, which are two important markets as well. But the big market is when we think about the U.S., we are 65% penetration in the U.S. So the big work that's happening right now is really into the community, and that's a very dispersed one. The good news is that we see 50% of our starts are in the community. So we'll continue reaching there.
And then the last piece, which is really an important one, is the duration of treatment. Now, usually in oncology, you see the duration of treatment is less when you get into the real world versus in the clinical trial. Here is the opposite. We are matching now what we've seen in the clinical trial and continuing. So we don't know when it plateaus, but it's still growing, which is great. So all these elements, I think, where we see the growth, not talking about the phase IIIs that are coming after.
Okay. I think on the slides, it's a duration of therapy is around 12 months.
Correct. Yeah.
Is that similar in the community versus kind of the academic centers?
I don't think we have the data that granular with the community. But if you think about right now in the U.S., 50% is starting in the community, which also speaks highly of the drug because you don't really get that as quickly unless you have a great safety, which we do as well. But I don't think we have it as granular. We have it by market or something like that.
Great. Maybe turning to kind of label expansion opportunities for KIMMTRAK. How is enrollment going in the TEBE-AM trial?
Yeah, I can address that, Jess. Accrual is actually going very well. So we're on track, as Bahija said, to finish accrual in the first half. We've got very enthusiastic sites, and we've heard very good feedback from the investigators we've spoken with. So on track for first half of 2026, completing randomization. And then we believe the final endpoint would be in the second half of 2026.
Can you remind us of the powering of that trial and what KIMMTRAK monotherapy and/or in combination with Pembro needs to show to be positive?
So Jess, we haven't specifically talked about the statistical analysis for the trial because we tend not to. But I will give a general answer in drug development that typically for survival in late stage, you want to see hazard ratios in the low 0.7-ish range, usually less than 0.75. Obviously, the lower, the better. But I think that that's really where we want to go. This is an indication where there's nothing really available. And in fact, we hear that a number of the investigators are even choosing chemotherapy, which doesn't really work, just highlighting the complete unmet need in this setting.
What do you expect the control arm to do?
So, historically, and I use the one-year survival as a landmark because that seems to be benchmarkable across trials. And so historically, the one-year survival is about 55%. And that actually takes into account even TIL therapy. It takes into account LEAP-004, which is a good metric. And it reflects the fact that although some of these therapies have responses that are durable, they're not impacting over 50% of the patients. And so that's why the median or the one-year survival is not really being moved. What we saw in our phase 1 expansion, which we did, is a one-year survival of 75%. And that was what really gave us confidence to start the phase 3 trial.
Okay. Maybe turning to PRAME, where does enrollment stand in the phase III PRISM trial? And how long do you think it'll take to complete enrollment there when we see the data?
Yeah, so we are in the initial ramp-up phase, which is standard for these phase three trials as you get global health authority approvals and sites' IRBs. So we've got dozens of sites activated, and I think we're going to hit that inflection point this year. We penciled in when we started around a three-year trial, so starting in 2024, potentially having the end in 2027. But I think later this year, as we enter a more solid cadence, we can project better when the readout will be. But right now, it's put in as a 2027 readout.
Okay. Can you also recap the data for brenetafusp that you provided in ovarian cancer back at ESMO? And how are you thinking about future development plans? When could we see more data? I think Bahija in the presentation talked about we might hear a decision on next steps for PRAME. Was that we hear in 2025 kind of the decision?
Yeah. Okay. So ovarian, basically. So number one, we had our ovarian data that we presented at ESMO. The drug is active as a monotherapy. That's clear. We do have some durable PRs. We do have disease control in a closed umbrella spider plot. Interestingly, and it's on our slide, we found that about 56% of the patients who progressed were treated beyond progression. This was really surprising to us because we were told that doctors within melanoma are very familiar with pseudoprogression and treating beyond progression, and it will never happen in ovarian cancer. But the majority of patients who had progression were treated on average for two months. So something interesting to note, it's telling us something. We saw CT DNA reductions in about or molecular responses in about one-third of patients.
We've talked about T- cell fitness in the blood being very important. That continues to be important for ovarian cancer too, and tells us earlier lines with better T- cell fitness are more likely to improve. And then we had preclinical evidence that chemotherapy not only reduces the tumor size, which we know is always good, but will also upregulate peptide HLA. And so we started a chemotherapy combination, and we saw very intriguing early data there. So what we learned from that initial phase I is we need to expand on this. So we're expanding in the platinum-resistant setting with chemotherapy combinations. And then we're moving earlier with Avastin because we think the path forward is, although it has monotherapy activity, the path forward is combination.
Now, in terms of what we want to see in order for the next step, on the one hand, chemotherapy in the platinum-resistant has very low response rate and very short durability. We're looking for something above that. But we've got to remember these are two active agents. And so ultimately, there will need to be some type of randomized trial. And I think the strength of the data will tell us what that randomized trial is. If it's very strong, we could do a phase three. If it's very intriguing, but it's not fully de-risked, we could do a phase II. Similarly with the Avastin. Now, in terms of what we're going to do is we're going to enroll that this year.
That's enrolling this year. And we'll be able to look at the data and make determinations on the next step. And when the data is complete and understandable, that's when we'll share the data. So we don't want to guide right now to a specific date or time. It's when the data is understandable and complete.
And was that for platinum-resistant you were talking about? And is platinum-sensitive kind of running on a lag to that?
No. Platinum-resistant and platinum-sensitive are running in parallel because they're two separate cohorts. The platinum-sensitive primarily is an Avastin combination. And patients are coming in with their best response on Avastin, so they will serve as their own internal control. So we'll look at what happens when you add on brenetafusp on top of Avastin. But a similar theme in terms of next steps.
Okay. What about lung? You talked about kind of this theme of trying to go earlier. It sounds like you're doing that in lung cancer too. When could we hear more on lung?
So, I think lung is very similar too. There, as Bahija noted, we're in the signal detection. We believe it should work because lung is T- cell sensitive. And in fact, when we look at the tumors, we actually see PRAME peptide HLA in the tumors. So we believe in theory it should work, although it's signal detection. As Bahija noted, we're going into earlier lines and combinations that make scientific sense for us. It will be in parallel with the ovarian and the same story. Once we have an understanding, we'll be able to share that data.
Yeah. Jess, I think we are in a phase where it is no longer we're going to go with time-driven when we're going to present something, but really data-driven when we're going to present, and I think we'll do the service to the whole community if we bring just data that you cannot interpret, so that's really our approach this time, and I think that's why I put it as a next 12-18 months. I think that gives us the.
Okay.
I think you have a question here.
And what about the half-life extended version, IMC-P115C? How's enrollment going in that phase one? And when could we see something there? And what do you want to see?
Sure. So the half-life extension started. We just had our first patient dosed, and that's going to continue to dose escalate this year. And our base case is it's a convenience. You can do less frequent dosing. It's an open question whether you're going to see more efficacy. We're open to that, but it's an open question. For us, Jess, the way we're thinking about it is we have brenetafusp in ovarian, brenetafusp in lung, and the PRAME HLE, which is essentially the same molecule as brenetafusp, except with an Fc. So these are all running in parallel now, and we're going to interpolate all that data in order to determine the next step.
This year, I would say with the half-life extended, it's try to get to a dose that or a dose range that is active and that we can confirm based on PK that less frequent dosing makes sense. And then we can combine all that and have the optionality in terms of what the next step is.
Great. Question in the audience?
Hi. Thank you. You primarily showed disease control with PRAME, and I'm curious, from the basic science perspective, PRAME is not a driver, but it's highly expressed, and I guess therefore you can either lose the target or lose HLA as an escape mechanism. How does this play in with your strategy? Are there other ways that you can target more durable responses? I know there was a thought maybe if you add CD4, other strategies to kind of get around this potential where you lose the target and therefore you could, it's a way the cancer gets around the therapy. I'd love to get your thoughts.
Yeah, it's a really good question, Dave. So on one hand, we're not sure that loss of expression of PRAME is the sole driver of resistance. And we're not also sure that loss of antigen presentation is also a major cause. It's still an open question. We think that there's essentially three components to this reaction. There's the T- cells and the T- cell fitness. That's one aspect. And one way to address that is moving earlier. We believe the T- cell fitness improves. Secondly is combinations. We do see primarily disease control, but we also believe with combinations, certain combinations will not only increase peptide HLA, but this disease control can add on to those responses that we see and build on top of those.
For example, in the PRISM-MEL, which is our first-line PRAME trial, some people say, "Oh, you'll just get disease control." No, we actually expect and think that we'll get higher response rates because you'll be adding our PRAME activity on top of nivolumab activity. Yeah, that's a very good scientific question and something that we're very interested in also.
Maybe turning to HIV, you've got an update coming up in the first quarter. So what's kind of the level of data detail we should expect? How do you plan to share it and how many patients are we going to see?
We announced at our third quarter call, we had treated 15 patients, five at three different dose levels, the highest dose being 300 micrograms. We announced that we saw biological activity. It was well tolerated. We decided that we would continue to dose higher. In order to do that, interestingly, we had to amend the protocol. It took a little bit of time. It's now out, and we're continuing to dose escalate. For this first quarter data cut for this first quarter congress, it's going to be about 15 plus or minus a few. We'll show the safety, but the activity there too. There's two important questions that we're asking here. Just as a reminder of the design, patients are stable on antiretrovirals.
We treat them for 12 weeks with our HIV bispecific, and then we stop both the bispecific and the ART. During the initial treatment phase, we're looking at viral reservoir reduction. So we're purifying CD4 T- cells and we're quantifying the level of RNA. No one has ever shown a reliable reduction. So we're looking to see, can we actually have a reliable reduction? And that will confirm that the mechanism works. Once again, no one's ever shown that before. Then when we stop the therapy, we'll be looking at viral rebound.
Historically, when you stop ART in these people, the virus rebounds within two weeks. You can already start to see the virus. It's a very aggressive virus. And by week eight, 98% of patients have pretty high levels of RNA. So we'll be looking at that viral RNA. Can we delay those kinetics?
So you mentioned you're going to go even higher with dose relative to what we're going to see in the first quarter. When should we expect that kind of next update?
So I'll take this one. I think the important thing is for infectious disease, I always like that because you don't have the target; the host doesn't have the target, right? We found ourselves; we thought if you think about KIMMTRAK is 68 micrograms, we thought with 300 micrograms we have a really good, but actually we didn't hit any DLT. That's why we're going even higher. The protocol that David talked about is already on. We are already starting to enroll the patients. We hope by the end of the year, that would be my guess, that we'll finish the whole thing and present. But it was very important for us and for the scientific community to present the first data set, and then we'll come with the full one.
I think what is also, once we have the dose, because we're not there yet, we would like to expand as well.
Okay, so just kind of thinking ahead and kind of what would represent an encouraging profile here, I'm sure avoidance of viral rebound and a meaningful proportion of patients would be exciting, but are you kind of trying to say the first step is just showing can you further deplete the viral reservoir?
Yeah, I'm happy to take a first stab, Bahija, and then you can certainly add on. So no one's ever done any of this before, so we're sort of pioneering it. I think for us, the analog I give, Jess, is the first immunotherapy trials with PD-1s. You wanted to see first evidence of activity. You didn't look for 50% complete response rates. You wanted to say the drug is active and there's something there and we can build on it. So for us, what we want to see in this initial phase one, and it's still dose escalation just to set expectations, 15 patients, is there evidence that the drug can do something, can touch the HIV disease?
Because if it can, we believe we can build on that. We can go to higher dosing. We can dose longer. There are combinations we can try. But really, can we get convincing evidence that we're touching the disease? Bahija, anything you want to add?
Yeah, no, I think this is exactly that. It has never been done before. We're charting new territories here. So I think any signal, whatever we see, and with the right dose, then we need to expand into more patients to be credible. So that's exactly the path that we're looking at.
Great. Let's see. I want to hit on some of the actually, maybe we can spend a minute on Type 1 Diabetes. I think you said there was a CTA coming by year-end, starting in the clinic in 2026. What's kind of the expectation for how this product would be used? Would this be kind of you take it chronically to kind of protect your Beta cells, or how does it work?
I think the idea is it would be initially in people who are newly diagnosed with Type 1 Diabetes, so they still have residual beta cell function, and that you would give some period of dosing, and that would prevent the progression and the requirement for insulin. This is actually a terrible disease if you know anyone with Type 1 Diabetes. If you can delay the use of insulin and preserve beta cell function. We don't yet have the target profile. Is it a defined period of time and then you get dosing a year later, or is it repeat dosing? I think we'll have to be driven by the data.
Okay.
But the goal is to delay full onset of Type 1 Diabetes.
When you move into the clinic, you would first start in kind of newly diagnosed patients?
Yes.
Because they still have a reserve beta cell function that you can protect. Ours is a way to protect and turn off these autoreactive T- cells.
Great. Maybe lastly on sticking with kind of INI and AD, I think you said it's running about like six months behind Type 1. Where would you picture a product like this fitting in the treatment paradigm? There's a lot of things patients can take for AD.
Yeah, so I think, again, we have to look for the data, but there is a possibility to be as well disease modifying as well, but we need between that and getting there, there is still a lot to see for the data. Because here we're blocking really both mechanisms. What we're going to be doing is showing more of the preclinical data that gives us a lot of encouragement. Where exactly compared to the others is the mechanism we're looking at right now as well?
I mean, I'll just add one other thing, Jess, is that we're hoping that this Langerhans cell that we're targeting is a very upstream node in triggering of many types of inflammation, including atopic dermatitis. So it's really one of the earliest upstream nodes that we're hoping to do. So initially, we may have to go into the refractory dupilumab refractory patients, but we're hoping this can really be an upstream disease modifier.
Okay. Okay, great. I think we're about out of time, so thank you.
Thank you very much.
Thank you, Jess.