Good morning, everyone, and thank you for joining us at our next session here. It is quite a packed room, huh, Bahija? But up here on our stage, I am very happy to introduce the CEO of Immunocore, Bahija Jallal. It's great to have you with us. Obviously, so many things going on at Immunocore. We were just talking before. Congratulations, you have one of the best performing IPOs in biotech over the last few years.
There was a big article in The Wall Street Journal, you were seeing, and that's obviously a testament to the ongoing success of your cancer drug, KIMMTRAK, which we're gonna talk about, as well as the potential, for your TCR bispecific platform, which is in an ongoing large, phase 2 expansion study, and many other indications possible as well off the platform. First, maybe I would just love to turn it over to you, and you could tell us a little bit about what you're looking forward to in 2024. Tell us about what's most important for KIMMTRAK this coming year, as well as, how you're feeling about the PRAME clinical trial, that will also be reading out in 2024, and that would give us a great segue into asking some of the more detailed questions.
Sure. Good morning, everyone. First of all, thank you for having me. I'm very happy to be here. Yeah, 2024, I think, is gonna be an exciting year for us. I think KIMMTRAK continues, like in 2023 and now in 2024, will continue to capitalize on, you know, the fantastic launch that the team has been able to do, so we're very happy. Just, if I focus on KIMMTRAK alone, less than two years now of launch, we are basically launched in 9 countries, and we are approved in 35 countries. So we're really happy with how we're trying to maximize the benefit in all the markets. In the U.S., we are 65% penetration in the U.S., so we'll continue.
So as you see in 2024, we will continue that penetration. As you know, in the U.S., we focused on, the big, academic centers first, and now we are in the community, and in the community, it's a lot more dispersed. So 2024, we'll see us putting more, more energy there. And then in Europe, we are thrilled with, you know, reimbursement and launch in Germany, France, and five new countries that we said we'll add this year. We added them already. We have an agreement also for pricing in Canada and Australia, so in 2024, you'll see us launch in Canada and, and Australia, and we'll continue. Europe is more, you know, country by country, negotiation by negotiations, but we will, we will continue there. So that's on KIMMTRAK and 2024, and, and really on metastatic.
But what's also exciting is that we are looking at KIMMTRAK in cutaneous melanoma. So the trial is ongoing, is enrolling really well, so we have announced the phase 2/3 beginning of the year or last year. So we will have the data for the phase 2 portion. We will finish the phase 2 portion in 2024, and we'll share the data, and the trial will continue into phase 3. And we just announced a collaboration with EORTC to do an adjuvant trial for KIMMTRAK, which I'm really excited about. These are for the patients who are basically at risk of developing metastasis, so going even earlier. So we hope in 2024, we'll be enrolling. So EORTC will be enrolling the patients. So that's-
Right.
That's on KIMMTRAK.
So, so to summarize on that, and I sort of didn't appreciate this coming out of your earnings announcement a week or so ago, which was that, the growth in KIMMTRAK for metastatic uveal melanoma continues in U.S. and country by country around the world. But in 2024, there are two important readouts, one of which is, well, let's say two, one of which is, cutaneous melanoma, randomized controlled phase 2 study.
Correct.
I believe it's on top of Yervoy.
So, no, it's basically a checkpoint inhibitor for-
It's on, it's on, it's on top of Nivo, or which one?
Yeah, Pembro, I think.
Pembro. Okay. So PD-1,
PD-1, yeah
... plus, KIMMTRAK versus PD-1 alone-
Correct
... in cutaneous melanoma with the primary endpoint of probably response rate, I would think. But, but a randomized controlled phase 2, so-
Yeah, we'll have for the phase 2 is a trend in OS, so we'll be looking at ctDNA and a trend in OS.
I think.
Um, yeah.
Okay.
And but-
That could expand the market by manyfold because cutaneous-
Correct
... melanoma is much larger than uveal, and that would be a strong readout that would support a phase 3.
Correct.
Okay.
So it's around 2,000-4,000 patients, and, you know, if the trend is positive and if it's, you know, the top line is positive, we can also at least try to go on the compendia, you know, or NCCN.
Right. That's right.
You think that randomized phase 2 could serve for NCCN guidelines, which could serve for reimbursement, and there could be growth in KIMMTRAK, and you could see that even before approval because of potential guidelines?
Correct.
Okay.
That's why we're hoping-
On this readout
... if positive, yeah.
Okay, and when is that data?
... towards the end of 2024.
Okay.
So the trial is enrolling well, so we should be able to have that.
Okay. And then in, just started, but EORTC is running an adjuvant uveal
Correct
melanoma study. That would take some time, to be fair.
It will take, you know, we assume, it's 300 patients approximately, so 150 in control, and 150-
Yeah
- patients. That should take approximately three years.
Okay.
And then-
Okay
... you have to count, we'll have the first,
Events.
Events-
Yes
that will be around 18 months after that.
Okay. All right. So, what's exciting about that is there is growth in metastatic and label expansion, which could significantly grow sales, I think by multifold, if cutaneous is particularly positive next year. Okay. Now, also coming up, leading you into this, talk about this important phase 2 PRAME program in solid tumors. Tell me about the status of that and the readout coming, and what are you looking forward to, and what's great data in the first half of 2024 for PRAME?
Okay, so PRAME is, we believe, a really great target. You know, it's homogeneously expressed in multiple tumors. And we have shown in ESMO last year that it's active in multiple tumors, and have, you know, several PRs and so on. So what we decided to do in 2023 was really expand basically into four indications that express
PRAME
... that express PRAME. Thank you. And also do a combination expansion. So it's pretty comprehensive program, and so we took the time to go more globally and open sites. So as you understand how many IRBs and so on to do. So that was really the majority of what we've done this year, and enrolling patients, obviously. So we had the first, you know, event happening basically is the cutaneous melanoma. We have said at the beginning that we are more likely to have more patients and earlier in cutaneous melanoma because that's where we did our first trials, and the cutaneous melanoma docs know this platform really well. We announced, I think in Q2, that we are starting a phase 3 in cutaneous melanoma for PRAME.
And so we shared at least just the durability of response that we saw from ESMO, so we then anticipate in 2024, we'll share the data. There were several points. Not only we've seen that the data, you know, continues to look good, the durability continues to look good. We also decided to go to first line because we know from our platform that, you know, if we look at in Keytruda, for instance, in phase 3, we had the hazard ratio is 0.56, but for patients that have smaller tumors that are around 3 centimeters, the hazard ratio is 0.36. So this, the earlier, you know, smaller is even better. So we actually are going, and we announced the phase 3.
So that trial, again, continuing into 2024, we hope to randomize the patients at the latest in Q1 2024. So that will go-
Right. So for the first, in PRAME, there will be an update on multiple tumor types in a phase 2 expansion program, first half of 2024. What was remarkable is that you saw this ongoing data, and you started a first-line phase 3 study, and you hadn't even disclosed to us the data from the phase 2.
So we used to do all that when I was in my previous in AstraZeneca all the time.
So you're looking at the data, but you said, like, based on the durability of the phase 1/2 from last year's ESMO, that it looks good, so that's what gave you the start of it-
Yes
... and some of the data from second line in this expansion.
Correct.
It's all second line beyond-
Yeah
but based on it, that's what you're-
Correct. Multiple points.
Yeah.
You never make a decision on one, but multiple points. We went to the FDA, we talked to investigators, and then that's how we started the phase 3.
Okay, okay. So cutaneous melanoma, and we'll get some of the expansion data, which is, I don't know, throw out a number, 20, 30 patients, or see response rates and durability at some medical conference or something in the first half of 2024?
First half of 2024, yeah.
Okay. And what other indications are also gonna read out in the first half of 2024?
We probably, you know, if I have to guess, it will be ovarian after that-
Okay
... because, you know, we're enrolling in ovarian. For lung, what we decided to do is to start with small cohorts. You know, first, let me just back up a little bit. We believe that T cell pathway works in lung. However, lung is heterogeneous, so you know, the EGFR mutant versus none and so on, that we wanted to look at the signal. So we started with small cohorts in lung before expanding in lung. So that will take a little bit more time, but it will come in 2024.
So are you implying that in the first half of 2024, there's less patients enrolled and less follow-up, so this disclosure in the first half of 2024, which is formal guidance of PRAME presentation, that lung cancer may not be a part of that presentation?
... as I sit today, probably, but we don't know. We'll know a little bit more towards the-
Okay.
you know, January or something like that.
Okay. And that it's heterogeneous, so it's more complicated, which is different patient population. So it's kinda like, let's figure out lung cancer.
Correct.
Let's look at that. Now, the other part that's going along with that, although that's the three main expansion cohorts, is you have a combination with PD-1.
Correct.
Is that just lung, or is that all of those indications also with PD-1 is also ongoing?
Yeah, so what we're doing with PD-1, and actually with all the combinations, so we have multiple expansions going in the combination. We know that wherever we go, if we go earlier, you have to combine with the standards of care. So in parallel, we are doing this combination to... You have to think about them almost like a safety run-in .
So we wanna do that. We know that our platform combines well with PD-1, so that's a given. Then we have other combinations with chemotherapy, KIMMTRAK, PRAME, and so on. So that once we have, you know, we are ready if we wanna go anywhere earlier.
Let me... so just to be clear, there are many arms of combinations-
Yep
... with PRAME-
Yep
... that, to be fair, since I've looked at this, hasn't been, it's just been talked about, a little bit secretive, but there's PD-1 combos, there's KIMMTRAK combos, there's chemo combos.
Correct.
All of that is ongoing in phase 1b's, because if you want to go to a big expansion, you had to show already that that was safe. So those are ongoing at the same time to make some big announcement in the first half of 2024 about what the next steps are.
Correct. So I'll just maybe add something. It's not really secretive, it just, it's not something that I expect or, you know, even if I see any efficacy there, you know, in combination, it has to be a randomized trial-
Right
... just to be rigorous. That's all.
Right. Right. Okay, fair enough.
Yeah.
Okay, so, what is great data in cutaneous melanoma when you put out this presentation? What is great data in ovarian cancer, and what is great data in lung cancer? Tell us, what would you be excited about, and what, like, what is good that would say, "I'm excited, we wanna continue to push this forward into more studies?" This is a phase 2 readout, 20, 30 patients in each arm. What would be good?
It's better than what's out there-
Okay
... what you compare it to.
Okay.
So that's where I'm gonna say, it depends on the indication, but that's basically what I'll say. You know, it depends, again, what you're comparing to. You have to be better, and you have to be not only, you know... Yeah, you have to see a good durability. That, for us, has always been really important as well.
Okay. Taking that step by step, so cutaneous melanoma, you've kind of already given us a hint, which is we're started a first-line study. That's number one. Would you do PRAME in second line as well? Would you cover that base? Or you said, "Look, we're already in first line, that's a higher probability of success. Your TCR bispecific platform works better there, so why would we start a Phase second line study when we already started-
Yeah, we-
... first line?
We're probably, we have.
That's right. It's reasonable.
Yeah, sorry. We do have several shots on goal for melanoma and with KIMMTRAK and with, you know... And I think we, you know, we made our choice where to go in melanoma.
Okay, right. Agreed. You've started a first-line study.
Yeah.
And by the way, can you just share with the audience what that first-line design was? Because, yeah, share with the design of that study.
Yes.
A pivotal study, I think that's pretty important.
It is a pivotal study.
Yeah.
You know, so it's a little bit complex because, as you know, by the time you have to always look at this, by the time we get there, what would be the standards of care? And, you know, in talking to the FDA and investigators and everything, obviously, there is Nivo LAG-3, will be, but Nivo LAG-3 is not everywhere. So Nivo LAG-3 is in the U.S. and Australia, I think. But outside, it's more Nivo, that's the standards of care. So we had to design, and I'm really grateful to our clinicians, they're fantastic, design the trial that will take into account the landscape once we get there. So it is, we'll have, as a control arm, Opdivo, so Nivo and LAG-3.
In the U.S., we'll recruit the patients in the U.S. for that, but the rest is gonna be outside of the U.S. with Nivo, but it's powered that you can see enough data with the Nivo LAG-3. We learned... And it's really important because we learned one thing with KIMMTRAK. We didn't do. We knew it doesn't work as well in the phase 3. Doing KIMMTRAK against Nivo plus Ipi, we didn't do that control.
Mm-hmm.
But when you come after, and even if you show the data, it's not the same as having the data. So we will have that with Nivo-LAG-3 in the U.S. and outside of the U.S., it's against Nivo-
Yeah
... just Nivo alone, but will be in combination with Nivo, obviously.
Well, let me ask this question. So again, the design of the study is if you're in the control arm, you get Nivo LAG or Nivo?
Correct.
Immunocore believes that the majority of the study is probably gonna be enrolled outside the U.S.-
Right
... so it's probably just Nivo for most, the majority of it. Now, I believe that in your active arm, it's Nivo plus PRAME. Well, obviously, Nivo plus PRAME could be Nivo. Is Nivo plus PRAME also gonna be as good as or better than Nivo LAG-3 in the United States? That could be 35% of the study. Now, you might say, "Well, Mike, it's that control arm average versus this, not powered to just beat Nivo LAG-3." Do you have a view as to whether your drug is better than Nivo LAG-3?
... Yes, so, you know, otherwise, you know, that's at least some of the hypothesis. Obviously, I'm a scientist. We have to do the experiments, and then we'll see. However, here are some of the things that why we believe that it we could be it. One is, you know, we go back to the principles of combinations, which is two- you have two monotherapies and, and, and two different mechanism of actions, and we do have with nivo and ours. So we are- we have a monotherapy with PRAME. LAG-3, if we compare LAG-3, and it's make the sin of comparing, you know, a cross trial, but if you look at PRAME is more active than LAG-3.
Okay.
So we believe that. So that I think the combination will work. So if we look at, especially in first line, you know, we don't like to look at the median. So if you look at the median, that's pretty, pretty, high. Why? Because the curves are biphasic, you know?
Yes.
when we look at the hazard ratio, which takes into account, you know, the activity in the entire curve.
Yes
... when you look at nivo plus LAG-3, the hazard ratio is 0.75 and-
Okay
... .81.
Okay.
So approximately. That's not a very high bar.
Yeah, against nivo alone. There's a 25%-
Right
... improvement in survival for nivo lag versus nivo, and you're gonna tell me that PRAME plus nivo, that survival data, I don't know, what'd you have, PFS data?
Yeah.
You think will be better than that versus nivo alone?
We believe that, but again, until we do the experiment, and if it's not better, then it should not be on the market. That's my point.
Well, I think you're gonna, again, just to the debate on Wall Street, because if this is positive, by the way, it's hundreds and hundreds and hundreds of millions of dollars.
Agreed.
Definitely would be great, and I definitely think you could beat nivo, which is a majority of the study. Some people believe that in the United States, where the standard of care is versus lag, you may be more similar. So even though you have a win on the study because you beat the control arm, the subgroup of the study will have had lag-
Yeah
... and it's not clear that's better. That's, you know, time to discuss that, but that's an interesting design of the study. Just wanted to point that out.
Yeah.
Okay. Let me, in the last few minutes, talk about some other programs. So while 2024 is a big year for PRAME, we just walked through a lot of that. We spent 15 minutes talking about that. A lot of readouts, first half of 2024, cutaneous, ovarian, lung. You also have an HIV study that's gonna have some data.
Yeah.
Just briefly explain that. And also, I hear that, Immunocore might be looking also at, autoimmune indications for-
Yes
... this platform, which is obviously quite exciting to drag T cells to treat autoimmune disease. Can you talk about both of that really quick in the last few minutes?
Yeah. So, one of the characteristics of this platform is really high potency, so it's in the picomolar. So that what we try to do in HIV, patients are very well controlled with antiretroviral, but they have to take their, antiretroviral for life, and so because there is a reservoir, and that reservoir is very, very, very hard to detect. So we believe with this technology, at least that's the question we're asking: Can we detect that reservoir and get rid of that reservoir, that these patients can stop basically taking, this for life? So what we've shown in the single ascending dose that we shared last year, I think, we showed that we actually engaged the target, which is a good news.
Mm-hmm.
And so we have the multiple ascending dose is ongoing. We will-
It's a peptide on the HIV virus, is that correct? On the cell.
Exactly. It's a Gag. Yeah.
Gag, okay.
Yeah, it's a Gag peptide. So we will, we will be asking two questions with the multiple ascending dose. The first one is, you know, can we detect the reservoir, and can we affect the reservoir and bring it down? And then the second question is, if we do that, can we, prevent the viral rebound? So what we're doing, we're dosing patients for 12 weeks with antiretroviral and our ImmTAV. We stop everything, and then we check for rebound, the viral rebound. So that's the data that we will bring hopefully in the first half of 2024. It's unprecedented, you know, but, could be really transformative if it works.
So yeah, so first half 2024, you're on... It's basically probably Biktarvy.
Yeah.
Yeah.
Yeah.
Biktarvy for 13 weeks. You add your HIV TCR bispecific on top of that.
Yeah.
I believe that would be 13 weekly infusions.
Yeah, twelve.
12, and then after 3.5 months, you take everybody off drug, and what Gilead told me, or any of your HIV experts will tell you, is that within a few months-
Yeah
... viral rebound could occur-
Yeah
... if you're not on Biktarvy. But if you're on Biktarvy and this drug, and this drug was basically able to get to the small little reservoir of-
Correct
... small HIV virus that is still around, that Biktarvy can't get rid of that last little reservoir, then your virus would rebound. And here, the T cell could kill the last reservoir, and you would not have rebound.
That's what we're hoping.
Yeah. So you will test this. So if we find out-
Yeah
... that even a proportion of the patients in this multiple ascending dose do not have rebound after... What is the follow-up time point on the endpoint?
So we have 38 weeks, actually.
38 weeks of follow-up?
Yeah, yeah.
That's what you're gonna report out?
But we'll, yeah.
Okay.
Yeah.
That's like, I don't know, 6, more than 6 months of follow-up.
Yeah.
50% of the people didn't rebound, even Gilead told me that would be remarkable.
Oh, that would-
Yeah
... be amazing.
Yeah.
Even if we delay, it will be amazing because it tells us... We took arbitrarily now the 12 weeks dosing, but if we see even a delay, you know, do you need to dose-
Yeah, yeah
... you know, more or something like that?
You could delay from having to take-
Yeah
... daily Biktarvy for six months, for example.
Yeah.
Yeah. Okay, so that's pretty exciting, and first half 2024-
Yeah
... of that data. Okay. And then-
So the autoimmune-
Autoimmune, yeah, just the last thing.
... autoimmune, I'm really excited-
Yeah
... about that. It's basically the opposite of what we do with oncology. So the first, you know, autoimmune is 80-90 different diseases, but a lot of these diseases are still handled with steroids. That means a sledgehammer on everything. What we're trying to do is to go organ specific and down-modulate the immune system or switch off the T cells. So the first thing, what we've done, and preclinically, we published the paper, so we have the proof of concept, is PD-1 agonist. So it's the opposite of oncology, so now can we switch off? And we believe this is working, so it's really, we have an agonist that works really well and that's very organ specific. So we will probably next year talk about the program. We will be looking at IND into next year.
So it's turning on PD-1-
Correct
... to turn on the brake-
Exactly
... to shut down the immune system-
Correct
Like, what would be a lead indication, for example?
You can imagine any indication that's driven by T-cell-driven indication.
Yeah.
The first one we will be probably trying is the Type 1 diabetes, so-
Type 1 diabetes.
Yeah.
Okay.
Yeah.
Exciting. All right. So we may have an announcement on that in 2024 as well.
Yeah.
So big updates in 2024 on PRAME, KIMMTRAK, HIV data. Looking forward to an exciting year together.
Great. Thank you so much.
Thank you, Mike.
Yeah.
Great.
You too.