Welcome, everyone, to the next session. I'm Michael Yee, Senior Biotechnology at Jefferies, and I'm very pleased to have members of the Immunocore team up here with us: David Berman, Chief Scientific Officer, and Ralph Torbay, the Chief Commercial Officer. Fantastic duo bunch because we're going to talk about revenues and sales and an approved drug in the commercial side, and we're also going to talk with David about the pipeline. That is fantastic. Maybe I would just have Ralph open up first because one of the great things about Immunocore is KIMMTRAK, which is on pace to do well north of $300 million. You've got a great orphan antibody that continues to grow in uveal melanoma around the world.
I would love to maybe just hear a little bit about your comments about the growth trajectory of KIMMTRAK and the durability of where that's going and the growth outlook for that this year. We can also get into some questions for David too. David, I got plenty of questions for you. Don't worry.
Great.
Tell us about KIMMTRAK, Ralph. Thank you, Michael. Thank you very much for having us today.
Yeah.
We have been doing very well with KIMMTRAK. As you could see from the first quarter results, we had $94 million in net revenues. That is a 33% year-over-year increase. It is actually our 12th consecutive quarter of growth for KIMMTRAK, which speaks obviously to how great the launch and the execution, and especially the medicine, has been doing for patients. We recognized a one-time revenue adjustment of $6 million, which came actually from very good news because we finalized pricing agreements with France and Germany. In the near term, we are very much focused on maximizing the growth in metastatic uveal melanoma. That means going a little bit deeper into the community in the U.S.
This is an area where penetration of uveal melanoma is not as dense, and therefore you have to go in a very methodical way. We still expect new launches. We're launching in 26 countries worldwide, and we expect a few more launches. We're prosecuting on these launches, which are also helping to drive incrementally the growth. Obviously, in the near term, we have TEBE- AM and the ATOM trials that we're very excited about.
In terms of the US, the growth outlook there, what % penetrated do you think you are in that market? Where are the drivers of that? I think that's community. Overall, in terms of how many uveal melanoma patients there are per year and what you are treating per year, what % penetration do you think you are? Can you get to those other patients?
Sure. We're roughly at 65% penetrated. There are roughly around 500 patients with metastatic uveal melanoma who are HLA-A*02:01 positive.
Yup.
HLA-A*02:01 positivity is around 50% of the patient population.
Okay.
I think the effort now is really going a little bit deeper into that community. A lot of these physicians actually treat cutaneous melanoma, and they're used to that. They see one uveal melanoma patient perhaps a year or every other year. It is about doing that just in time. That is a lot of the work that we're actually committed to doing today.
So just to be very specific, SG&A and Salesforce going out to the community, educating them, because while they may only treat a couple per year, they need to be aware of the drug in order to get it. About 60% penetrated.
That's right, 65.
Yeah, steady growth.
Steady growth every year.
OUS, yeah, that was a big thing last quarter. You actually had a positive adjustment because the price in France and.
Germany.
Germany were agreed upon. It actually ended up being slightly higher, more value versus what your accountants had had. There was a positive adjustment versus what you're booking. How is the growth there? What were you doing this quarter? Do you expect steady growth because there's new launches in some countries?
Yeah. We have new launches in the U.K. and Poland. Actually, U.K. and Poland were both launched in Q4, Netherlands in Q1.
Okay
There we are right in the middle of launching. Germany and France, actually, interestingly, we are still seeing growth. That growth is coming through marginal penetration. We are above 80% in both of those countries. That being said, we still see duration of therapy growing there. We are now working a lot on finding patients earlier because if you find patients earlier, they will do better and obviously stay longer on the medicine as well.
Where is duration of therapy now on this drug on average, either in the U.S. or outside the U.S.?
It's around 12 months, which is actually very impressive when you consider the clinical trial data. For me, I mean, I've launched many drugs in oncology. This is the first time I see a drug doing this well in the market, especially doing better than what we've seen in clinical trials.
Clinical trials, it was remind me what the number was.
It depends on the follow-up, of course. Around this time, we saw around 10 months.
Yeah. It was 10 months. And actually, the duration of therapy is 12 months. That's because people are continuing on the drug even past "radiologic progression" or what's going on there and why are docs continuing to keep them on.
Yeah, that's right. That's exactly what's happening. In the clinical trial, we actually had to, at some point, call the progression. That's after two scans that showed more than 20% increase using RECIST. That's when we called progression. You had to do it per protocol. What we're seeing in the real world is actually physicians are keeping the patient on, potentially using radiation therapy, surgery in some instances to help with some of the growing lesions. Really, they're seeing patients do very well and benefit long-term. Hence why we're seeing, I think, a better duration of treatment in the real world.
Where do you think that could go? Twelve months and they're treating past radiologic progression. Where can that go?
We're hoping it will continue to grow because that means good news for the patients. They're benefiting from it. That being said, we are seeing it moderate in certain countries, like in the US and some of the more mature markets. As we enter our fourth year of launch, we're seeing that duration of therapy.
Let's put it this way. There's not like another approved drug or another option for people, technically speaking, on this. I'm not saying that they're taking it all the way to average overall survival. I guess I'm just trying to figure out why would usually they don't treat past that progression. This has been a key part as to why you're continuing to see, other than more patients, but people are keeping them on drug longer because doctors see value in the drug.
Yeah. I mean, they're seeing value in the drug. They're seeing the patients. And at least what we hear is that the patients are doing well. They have lesions. The lesion is still there. But the patients are doing exceptionally well. They're living their life. So really, that's one of the reasons they're keeping the drug.
There also may be an element, Michael, of earlier screening now that there is a therapy for the metastatic setting, whereas before there was not. Some countries have more robust screening to detect earlier metastatic lesions.
That's interesting. You think that they're getting on earlier in their first line?
Yeah.
This is first line.
I think in some countries that could be an explanation.
Interesting. Okay. All right. That continues to be strong and steady growth. That has been one of the key factors to demonstrate success for Kimmtrak. There is some potential perceived competition in uveal melanoma. Another company, IDEAYA, was here. They are talking about how they will have phase III data for their oral therapy in first-line melanoma, HLA-A*02:01 negative, but also that they plan to do positives and also that they have been treating people in HLA negative and positive and are going to have survival data in phase II at a conference. A new therapy is coming, potentially. How do you help investors walk through the differences between those and appreciate that it is definitely possible that another drug could be approved in uveal melanoma?
Michael, as you said, the other medicines are in HLA-A*02:01 negative. That's where they're being studied. That being said, we take competition very seriously and obviously make plans around it constantly, whether this one or any other competition. I think the important piece to keep in mind, especially when thinking about Kimmtrak, is really this is unprecedented. This is the first approved medicine for HLA-A*02:01 patients in over four years in uveal melanoma. We've established long-term survival at three years. In fact, it was published in the New England Journal of Medicine. We saw two very interesting aspects of this. One is unprecedented survival at three years, but also the fact that in the long term, we see adverse events actually improving. We see the safety profile with CRS is predictable at the beginning. Then over time, the adverse event profile improves.
I agree. Extremely well-tolerated drug. I thought that the overall survival that people quote for your drug is 20-something months. That's in the label. Are you referring to a different overall survival?
There's a 22 months, which is the median overall survival, as you said.
Amazing.
That went from 12, right? So almost doubling of the median overall survival. In fact, the hazard ratio was 0.51.
Yep. So 22 months.
To 22 months. At three years, it's 27% of patients who are alive, which is unprecedented for this disease.
Landmark analysis. In three years, there's still one quarter of the people are still on.
Yep. That's right.
Okay.
Yeah, I mean, I think, and beyond that, when you think about the fact that this is not only standard of care, but it's also the most prescribed medicine across major markets, I think between the patient component, they care mostly about overall survival and the fact that this is in the practice.
Well-tolerated.
It's going to take a lot to displace Kimmtrak.
Okay. Yeah. I mean, we're prepared for some of these updates from the competitor. So again, different HLA subtype. And also you have a super long demonstrated survival. You've been on the market. Good standard of care.
That's right.
Now you're also trying to, here's where we could talk about and bring in David as well, because there's the opportunity for Kimmtrak to, in our analyst estimates, more than double sales opportunity because you're also in a pivotal phase II/III for cutaneous melanoma with KIMMTRAK. This is in combination. Can you talk about the design of the study and your confidence that this randomized controlled study could work? I believe the data is coming second half of next year. This could be positive, and this could more than double or triple because cutaneous melanoma is definitely double or triple the uveal melanoma. What do you think about that, David? That could work?
Yeah. So just as a reminder, we started it as a phase II/III. Last year, we converted it into a standard phase III. The three arms, patients who are previously treated on anti-PD-1, CTLA4, and BRAF targeted therapy with BRAF mutant, so nothing really available, are randomized to Kimmtrak versus KIMMTRAK plus pembrolizumab versus a control arm. The key thing here is that the primary endpoint is overall survival. This is going to be the first phase III trial, if it's positive, to have an overall survival readout in late-line melanoma. It plays to the KIMMTRAK k strength. I mean, it's a GP100 positive tumor, like uveal melanoma.
In the phase I and the phase IB trial in checkpoint combination with KIMMTRAK in cutaneous melanoma, we saw the same metrics that we saw in uveal melanoma, which is a modest response rate, but very promising overall survival. In fact, the survival we saw in late-line cutaneous melanoma, the one-year survival was 75%, the historical one-year survival being 55%. That is what gave us confidence to run this trial. We are asking really two questions. Does PD-1 add to KIMMTRAK? The other question, of course, is, and the most important one is, is Kimmtrak better than whatever else is available out here with overall survival? That trial is accruing well. It is still accruing well. The target is to have that completely randomized in the first half of next year.
The readouts, which of course is event dependent, could be in the second half.
Can I ask a question on the design of that? I recall the three-arm design.
Correct.
At one point, we believed that because there are two Kimmtrak arms, one is Kimmtrak monotherapy.
Correct.
One is Kimmtrak plus PD-1.
Correct.
One is a dealer's choice.
Essentially. I can go into it, but it's essentially dealer's choice.
In dealer's choice, there's not a lot. I mean, there's like old chemos. There is Iovance. And there is what else? Is this a relevant study? Because in your combination, you're getting PD-1. Didn't people get PD-1 in the first line?
Yeah. So in this setting, there's nothing really available. I mean, Iovance was, Amtagvi was recently approved only in the US. Interestingly, most of our approval is outside the US.
The point of here, just to be clear, is that that's early in the adoption. That's not really going to be a big part of the control. Is the point of this trial?
Exactly. Typically, what doctors will do in this setting is they will retreat with PD-1s. They will retreat with BRAF, even though they do not expect much benefit. They will give chemotherapy because nothing else is available. They will put them on clinical phase I or phase II clinical trials. That is really all that is available.
Those are allowed in the control arm?
They are allowed in the control arm. The reason is, this is why it's novel, is because we have a survival endpoint. As long as you follow them for survival, they can leave our treatment arm on the study and go into subsequent studies.
Okay. What do you expect? Again, there are two Kimmtrak. I'm sorry. Have you merged that into one? Have you dropped an arm? Have you moved to a one versus one now?
Yeah. No. So it's still three arms. The original design of the phase II was to pick one of those arms to continue.
Right.
To only have two arms in the phase III part, the control and a Kimmtrak arm. Because of the accrual patterns, the survival would not have matured to allow us to choose one of the arms. We just converted the entire study into phase III and decided to run out both KIMMTRAK arms in parallel. Yeah. We will have a KIMMTRAK plus PD-1, a KIMMTRAK monotherapy, and then the control arm. Essentially.
That's interesting.
Two KIMMTRAK arms and one control arm.
That's interesting. Okay. And all of this is based on the phase I/II open label data where there was a combination and you basically saw a, what, 75% survival at 12 months?
Correct.
Okay. Have you followed those patients out for median survival?
No. The study ended a couple of years ago. There weren't that many patients on to go beyond that to go with the continued follow-up. The reason I landmarked to one year, 75%, we did follow it to two years, by the way. The reason I landmarked to one year is because if you look at all of the other historical trials that are out there, they typically are only robust up to one year. There are very few follow-up patients beyond one year because there haven't really been phase III trials in this setting. They're typically smaller trials. I felt one year is a still robust endpoint to compare to historical trials.
Okay. All right.
That's the reason I anchored to one year.
Again, the next milestone is completion of enrollment by first half 2026. Obviously, we're currently in the middle of 2025, so we have some time to go. But you feel it's been enrolling well? This is like mostly outside the U.S. or what?
Yeah. It's mostly outside the U.S. So we do have some good U.S. participation. But like all melanoma trials to date, it's mostly enrolled outside the U.S., Europe, Australia.
Okay. And yeah, this is obviously for HLA-A*02:01 positive.
Correct.
This is second-line cutaneous melanoma. And there's not a lot of options.
Correct. Yes.
Yeah. Okay. All right. So we'll look to that. That could be a huge upside opportunity because cutaneous melanoma is two to three times the size. What about obviously PRAME, right? PRAME, this is a bit of a slightly sore spot for us because while you're continuing to execute, Wall Street is definitely scratching their heads about the overall probability of success of this. You've presented data at last ESMO and ASCO, ASCO, ASCO and ASCO. The point about it is you have pushed forward to a phase III randomized controlled study of PRAME plus PD-1 in first-line melanoma. Talk about the design of this study and what gives you confidence that this study will be positive.
Sure. Before I talk about the design, I just wanted to mention we also have the adjuvant Kimmtrak trial, which I'm pretty excited about. We can talk about that also.
In uveal.
In uveal.
In uveal. In uveal melanoma II, you're going earlier.
Exactly.
That is reasonable.
I just wanted to round out the Kimmtrak before we move to PRAME.
Okay. Great.
Yeah. With KIMMTRAK, I think there were several factors which led us to move to the phase III trial. One is we know that our platform works in melanoma. Number two, the Kimmtrak monotherapy data that you're referring to that we shared at ASCO.
ASCO monotherapy.
At ASCO last year, we benchmarked that to what we consider a very relevant population, which was Nevo plus Lag 3 in Relativity 20. There we felt that the monotherapy KiIMMTRAK data was superior cross-trial comparison to the Nevo plus Lag 3. The disease control rate was higher. Number two, if you look at the spider plots, we've talked about this interesting phenotype of a closed umbrella spider plot where most of the patients have disease stabilization that looks like a closed umbrella. If you compare that to the Relativity 20 spider plot, which is more of an open umbrella, which is typical in phase I, you have some DPRs, but then most of the patients tend to progress. It does appear to us that as a monotherapy, KIMMTRAK in a similar line was superior to Nevo plus Lag 3.
That's interesting.
The second was that we showed that T- cell fitness improves as you move into earlier lines. In fact, the median PFS was six months in patients who had a good T cell fitness. We know T cell fitness improves as you move to earlier lines. The third point was in the first-line trial, we are now combining Kimmtrak, which has definite monotherapy activity, the different mechanism, with nivolumab, which of course also is an active drug. It is nivo plus tebentafusp versus n ivo. The n ivo cancels out. You are asking, is t ebentafusp going to add anything on top of that?
Yes. So think about that. So I think Wall Street typically loves to see response rates, huge tumor reductions, spider plots that all go down. And you did have some RECIST criteria overall response like 13%.
Yeah.
There were some sick patients in cutaneous melanoma, metastatic melanoma. You had a lot of stable disease. You think overall that that's obviously had, I'd say, biologic activity.
Yeah.
That's point one.
Yeah. And I'll say actually two points, Michael. The first is, yeah, we did have about 11% RECIST PRs. Interestingly, we had an additional, I think, 15%-16% of patients had tumor reduction that was still called SD, but had the same durability as a PR. And we saw that exact same phenomena in Kimmtrak. We are now talking about 28% of patients are having definite evidence of drug effect. Yeah. The other point I just wanted to remind everyone is although Kimmtrak is a survival drug and had a great survival benefit with the 0.51 HR, it also met statistical significance for PFS. The PFS hazard ratio, I think, was about 0.72 of KIMMTRAK versus essentially pembrolizumab in first-line uveal melanoma. This is still a platform that can deliver a PFS benefit.
Right. Right. Even if you go to KIMMTRAK, which everyone agrees is "low response rate," you already saw a positive PFS because you're stabilizing the tumor.
Exactly.
That was 0.77 hazard ratio versus Keytruda.
That was 0.73.
0.73. People on Keytruda were still progressing. The tumors are getting larger, even in a drug that has modest stabilization. Going back to PRAME, on PRAME, you're saying there's great stabilization of disease. That's point number one. Point number two is that you're going earlier.
Exactly.
Okay. And then point number three is you're in combination. If you're going earlier and then you're adding on top, you believe, yeah, you believe with PRAME that that would drive a PFS, puts a primary endpoint.
It's PFS.
PFS.
I do believe it will drive a PFS benefit.
Yep.
I do think there's the potential also to have a higher RECIST response rate. We haven't shown that, of course. I think there's the potential because we are getting 28% of patients are having tumor reduction.
You're a healthier patient too at first line.
Exactly.
Yeah. Now, you know overall response rate won't be the primary. We're going to have to deliver PFS.
Exactly.
Do you need to deliver overall survival in melanoma?
In first line, we would like to see a trend. We'll have to follow the patients longer. It's just that survival is very long in first line. For regulatory approvals right now, PFS is accepted. Of course, you follow it as a secondary endpoint for overall survival.
Okay. Tell us where that is because we're going to have to wait a little bit. That is enrolling. Tell us about where that is.
Yeah. So that's randomizing nivolumab plus tebentafusp versus either nivolumab monotherapy in some countries or nivolumab plus Relatlimab.
Yes. Let me clarify that. Yeah. That's important.
We started that trial last year. As I've seen in all my phase III trials, there's an initial slow ramp-up phase while you get countries activated and sites activated. Then there's an inflection point. I think we are at that inflection point now. We have between 100 and 200 sites already open globally.
Yup
We're on track this year to have the IDMC complete their efficacy and safety review of the first 60 patients treated with tebentafusp to choose the dose to continue. If you remember, there was a dose selection by the IDMC who will review the first 60 patients treated with tebentafusp plus nivolumab at dose one and tebentafusp plus nivolumab at dose two. There were two doses.
When is that? I mean, is that a Project Optimist thing?
Yes. It was Project Optimist.
Is there an interim on the first 60?
It's the first 90 patients.
First 90.
And then 60 of tebentafusp.
I have another company that just kind of had that run-in period and they picked the lower dose. When does that occur?
That will be in the second half of this year. We're on track for that.
Is there any futility analysis or what? What are they going to look at?
This analysis is strictly looking at the tebentafusp arms because we agreed with the FDA no alpha would be spent.
Okay. They will pick it based on looking at it. It's sort of interesting. They look at safety.
Yeah.
What are they looking at to pick?
Yeah. So they'll look at efficacy, of course. So they'll be looking at RECIST-based efficacy.
Resist criteria.
Because at the end of the day, this is a PFS endpoint. They'll be looking at RECIST efficacy. They'll be looking at safety, which is essentially CRS for the most part.
Okay. Okay. So that's coming later this year. We'll look for that. There shouldn't be any futility. It is high dose versus low dose.
Correct.
What do you think? Based on the data, I can't remember the data, between high dose and low dose. Do you think that the high dose would go forward?
We're open to whatever is the best data. I think in our phase one dose escalation, we didn't really see much dose response. We saw a step, which is no activity and then at 20 micrograms activity. We didn't really see a strong dose response above that.
Okay. Okay. And then we marched forward. Now, how many patients are in the study? Are going to be enrolled?
Sorry?
What's the target?
It's about 650 patients through 25 per arm.
Three on average per site. That is not how it works. You have 200 sites open. You feel pretty.
Yeah. No, we have between 100 and 200 sites.
100 and 200 sites. Okay. All right. So when does that complete enrollment? And then when is data?
Yeah. So currently, we put in when we started a three-year trial just because that was the benchmark out there. I think later this year, once we have in steady-state randomization and we get a better sense of event rates, we can project that. Right now, we're penciling in a three-year trial. Maybe end of 2027.
Okay. Okay. So that is interesting. Again, I'll repeat that. It's interesting also because the control arm is Keytruda in most countries outside the U.S. But here in the U.S., they will be getting Relatlimab.
Yeah. So it's actually Opdivo.
Opdivo. Here, it's not Keytruda. It will be Opdivo.
Yes. Opdivo.
That's interesting.
Right. So it's Opdivo monotherapy or Opdivo plus Lag 3.
Thank you. Thank you. No Keytruda. Thank you. That's the other company that's running the phase three. Okay. That's great. You also believe, obviously, in the US that you believe, while a little bit harder to handicap, at least in the United States and certainly with this FDA, they're going to look at this, that you believe you'll beat Lag combo as well?
Yeah. We expect to, based on what I call the apples-to-apples comparison. Yes. I think commercially, we need to show at least a point estimate showing that we're better than Nevo plus Lag 3.
Right. At least a trend. Yeah.
Exactly.
Then hitting on the overall. Okay. We will continue to follow the execution on that. That is super important. Maybe in the last two minutes, I would love to ask a little bit about the additional pipeline things. I am actually going to skip over the other PRAME indications, if I may,
Sure
because we have a new target, PWIL. Did that file an IND?
Yeah. PWIL filed actually a CTA. It started in Europe.
Okay. This is a novel TCR bispecific.
Yeah. This is a TCR bispecific targeting PWIL, which is a novel target, essentially expressed in colorectal cancer, gastric, and pancreatic. It is not really expressed in normal adult tissues except for the testes. This is already in dose escalation. It is moving well. Of course, CRC is a huge unmet need.
Yeah. When can you get data?
Potentially next year, I would say. Of course, it'll be data dependent when we have a complete data.
You know what's good about Immunocore is you guys do not do piecemeal, piece-drop phase ones. You guys always put out a whole slew of amount of data and therefore multiple cohorts, not just like the first cohort. I would think ASCO of next year is probably reasonable.
Potentially.
Yeah.
Potentially.
Okay. This is single agent. You'd expect responses and that type of stuff with this type of mechanism? What would be expectations?
Yeah. I mean, it's an open question. Is this going to be more like a Kimmtrak or is it?
Colorectal is tough.
Colorectal is tough. Although late-line colorectal, you know it's essentially single chemotherapy has single-digit response rates.
Yeah. It's a cold tumor. It's hard to, overall, it's a tough tumor. I'm just saying response rates, we'll look at the totality of the data, obviously. You have a second program. I'm going to say infectious disease, HIV is one that would matter. Do you think that that's the one we should highlight here in the last 30 seconds? When's the next data? Because that was interesting.
Yeah. HIV was exciting for us because it told us at least that this platform can touch the disease. We're not yet at the target product profile that we want. We're showing that we can actually have an effect on the virus. We have HBV data that will be coming out later this year, single ascending dose data. Not multiple, but single. I think when you put that data together with this data, we'll begin to ask, can this platform reach the reservoirs?
When's the next HIV data?
The HIV is continuing dose escalation. And then we'll do an expansion. When that data is complete, we'll show it. I would say potentially next year also.
Okay. Look, we looked at the first data. It definitely has biologic activity. There's promise there. You were seeing all the biomarkers. And also a number of people were able to stay off antiretroviral therapy. So more N would be needed. But you're continuing to dose forward. All right, guys. Thank you very much. Appreciate the update. And thank you very much.