All right. Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research Team. It's my pleasure to host the management team of Immunocore, and we have with us today, EVP of Commercial, Ralph Torbay. Thanks very much for joining us.
Jonathan, thank you for having us. It's been a great conference so far.
Would you please briefly just take a few minutes to introduce the company?
Sure, I'd be happy to. Immunocore really pioneered T-cell receptor technology by creating the first solubilized T-cell receptor. We actually also pioneered T-cell engagement in the solid tumor. KIMMTRAK was the first T-cell engager in a solid tumor.
Now with the 5-year overall survival, will be the one from a Phase 3 study with the longest overall survival in a solid tumor. Very exciting days ahead for Immunocore. It's also a commercially integrated company with the launch of KIMMTRAK and 5 years ago. We're developing our platform in autoimmune infectious diseases and oncology.
Great. Thank you for the introduction. Can you discuss, start with the commercial accomplishments with KIMMTRAK to date, and where do you see this going in the future?
It's been an exciting runway for KIMMTRAK so far with last year we delivered $400 million in net revenue. This was a 30% year-on-year growth. It was actually our fifteenth quarter of continuous growth, which is exceptional and, you know, all kudos go to the team. We're also 70% penetrated across all major markets.
We are launched in 30 markets and really KIMMTRAK is the standard of care across all HLA-A*02:01 positive uveal melanoma patients. From here, we expect to incrementally continue to grow. Of course, it's our fifth year in the market, so we expect that growth to moderate. This, you know, moderation, we were growing at 4%-7% quarter-on-quarter.
We expect some quarterly variability, but moderating from that 4%-7% that we've talked about in the past.
Got it. What would you say are the key learnings to the KIMMTRAK launch to date?
There's a few learnings, of course, this being the first T-cell engager in a solid tumor. Number one was very much around the adoption of KIMMTRAK. As you'd expect in the community where for a rare disease, it's oftentimes more difficult to adopt, especially when the physician is seeing one or two patients every other year. We developed actually a lot of capabilities to be able to go after the one-off patients in the community, a lot of predictive analytics, actually.
Another big learning for us was looking at the duration of therapy of KIMMTRAK. This is, for me, this is the first time I see a medicine do better in the real world than it does in clinical trials. We have 14 months mean duration of therapy in the real world. Just overall, the adoption of KIMMTRAK has been really strong and a standard of care today.
All right. you've guided to publishing long-term survival data with KIMMTRAK in metastatic uveal melanoma. can you help us understand, sort of help us set expectations for these data and what is the importance of this update?
Yes. This is a very exciting year for KIMMTRAK for several reasons. One is we published recently in December at ESMO, the 28-month median overall survival for KIMMTRAK in 152 patients from a French registry. Very ex citing because you can see how that's increasing the bar for overall survival. One of the conversation that we were having is, does this improvement in mean duration of therapy, does it translate in overall survival?
At least in France, it seems to be the case. We're also publishing data in the U.S. from real world evidence, now that we're 5 years in the market where we, you know, hope to see a similar trend. We have our 5-year overall survival data from our Phase 3 study.
That is exceptional because patients. In fact, I was talking to the investigator from that phase three, and he was telling me, "Ralph, do you realize that we've never had 5-year overall survival data in metastatic uveal melanoma? Patients did not live this long in the past."
Now we're finally having that conversation because we have KIMMTRAK. That's the second piece of data that I'm very excited about. Lastly, we have our TEBE-AM study, of course, reading out as soon as the second half of 2026.
Great. before we get to TEBE-AM, how do you see the competitive landscape in uveal melanoma evolving? what are the implications do you think to KIMMTRAK?
So far, I know of one Phase 3 study in HLA-A*02:01 negative patients, and of course, this is a high unmet need setting because KIMMTRAK is not approved in that setting. Good news, I hope that study is positive because it, you know, would be great news for those patients.
Of course, from an HLA-A*02:01 positive perspective, there's mostly early clinical research, but not much to speak of in terms of registrational studies. I'm actually particularly excited about liver-directed therapy because that could be a good modality, especially now that it has been shown that systemic therapy with liver directed can improve outcomes. That's something I'm excited about, and we have clinical trials ongoing.
Got it. Maybe now switching over to TEBE-AM in a cutaneous melanoma setting, can you tell us about that study and what are the timelines associated with that study?
Sure. This is a very exciting study, mostly because this is an area of very high unmet need for patients. These patients, the median overall survival is roughly 13 months, roughly one year. Very high unmet need is that patients who have progressed on checkpoint inhibitors. With TEBE-AM, which is a life cycle management study for KIMMTRAK, we expect to finish enrollment in the first half of this year, then data as early as second half of this year.
Got it. What are the reasons for confidence in that study, leading to a positive result?
The reasons for confidence are that we have seen in our Phase 1/2 study, so we had a Phase 1/2 study in combination with checkpoint inhibitors. From that study, we pulled the patients out that really matched the patient population from TEBE-AM.
When we looked at the overall survival for those patients, it was actually 75% at one year, which is obviously exceptional because when you look at most therapies in this space, in the late, post-checkpoint inhibitor space, most of them have shown 55% overall survival. Even TILs have shown 55% overall survival at one year. This is very exciting for us, and that gives us proof of confidence to go into this Phase 3 study.
Got it. How should we be thinking about what patients might see in the investigator's choice, control arm for that study?
Great. Good question. We're obviously not looking at the study data itself, but when we look at what's happening in the real world, first of all, most of these studies are in cutaneous melanoma are accrued in Australia and Europe. That's the majority of where these studies are accruing patients.
When you look at the center of care in a lot of these geographies, you see retreatment with checkpoint inhibitor, retreatment with BRAF/MEK, and some chemotherapy and clinical trials. By the way, in the U.S., we see similar things, maybe with one or two exceptions of additional therapies like TILs that were recently approved. For the most part, that's what we see, and that's what we expect to see in the control arm.
Got it. How do you guys view the commercial opportunity for KIMMTRAK in cutaneous melanoma?
This is a significant commercial opportunity for us for two reasons. One is very high unmet need. This is 4,000 patients or up to 4,000 patients with late-line cutaneous melanoma without almost any option. Here KIMMTRAK has the TEBE-AM study is an overall survival endpoint.
KIMMTRAK is an off-the-shelf therapy, and it's a therapy that is familiar to at least half of the physicians that treat cutaneous melanoma. There's a good familiarity base, and from a pricing perspective, lastly, given that this is unmet need, if the overall survival is positive and we can potentially have a similar pricing premium in cutaneous melanoma.
Got it. How would you compare the competitive landscape in cutaneous melanoma to uveal melanoma? How does that, you know, impact your thinking on where KIMMTRAK could fit?
The cutaneous melanoma setting is more competitive in that today there are TILs are approved. There's also retreatment as well. but KIMMTRAK has really, I think, a huge advantage over every other competitor in that this is an overall survival endpoint. While others are talking about response rate, we're going to be talking about overall survival.
While others are focused on certain, in certain centers because you need chemolymph depletion or surgery, or, you know, or lesion injections, we're actually off the shelf. We're familiar to physicians, so I think we have a great foundation from an adoption perspective, and if the data is positive, we would have a good foundation from a claims perspective.
Got it. What has the physician feedback been like for what the product profile could look like for KIMMTRAK versus some of these other options?
So far, the feedback has been very good. Around 50% of patients treated with cutaneous melanoma are treated with physicians who are experienced with KIMMTRAK. We're hearing both from them and the investigators that KIMMTRAK, you know, from a safety standpoint is exceptional.
You see a lot of the AEs happening at the first three cycles, and that is mostly CRS, and then very tolerable after that. In cutaneous melanoma specifically, you know, people are very excited about this being a very different modality from checkpoint inhibitors because obviously checkpoint inhibitors in this line of setting don't work.
All right. You mentioned the overlap in the physicians. Are there other learnings you think from the KIMMTRAK experience that are important for cutaneous melanoma from uveal to cutaneous?
Yeah. I think there's quite a few learnings. One is treatment beyond progression. This was something that we saw in uveal melanoma where investigators came to us and said, "Hey, you know, I have patients who are progressing. I'd like to keep them on because they still seem to be benefiting from KIMMTRAK, and their progression's not fast enough that I'm concerned."
Or maybe it goes up and down, or maybe there's an additional lesion that they address with radiation therapy. A lot of those learnings are portable, I think, to cutaneous melanoma, where I think this phenomena is also happening. That's one interesting point. The second piece is really from an adoption perspective, we've seen great adoption in the community in uveal melanoma, right?
you know, we have 70% of our prescriptions are coming from the community. Half of our new starts are coming from the community. it's about, you know, a lot of learnings that we derive from there on how to educate community physicians to be comfortable adopting a T-cell engager. We're gonna pour that into cutaneous melanoma as well.
Got it. What would you say are the geographic considerations for KIMMTRAK, both for the clinical development in cutaneous melanoma as well as on the commercial front?
From a geographical standpoint, obviously, the U.S. is our main market. That's probably going to be our first market to launch. You know, we plan to launch in all the markets where we currently are, and there, you know, it's similarly high unmet need. This is a global study as well, so it would support this global launch. You know, data dependent, but, you know, we're very excited about having a, you know, global launch coming up soon.
Understood. Maybe switching over to the ATOM study in an adjuvant uveal melanoma. Can you talk about how you're seeing the opportunity in this setting, and what are the timelines for that study?
Sure. When we looked at the ATOM study, the reason EORTC came to us and worked with us to pursue this indication is because we saw in our Phase 3 data in metastatic uveal melanoma, we saw a 0.68 hazard ratio for PFS in patients that had less than 3 cm lesions. Obviously when you take it into the adjuvant setting where patients have micrometastasis, right?
Non-visible lesions, there was the belief that this could have a transformative effect for patients. Upon that basis, we worked with the EORTC to launch the first, the only ongoing Phase 3 adjuvant study in this setting. We expect that to be to accrue in the next 2 years, and then data 12-18 months after that.
Got it. Maybe we'll switch over to PRAME and brenetafusp. Can you talk about the Phase 3 study in frontline cutaneous melanoma, and reasons for confidence in that study?
Yes. This is another study I'm very excited about because we saw with PRAME in the monotherapy setting in late line cutaneous melanoma, we saw really quite significant disease control rates. In fact, when compared to Opdualag in the same setting, we saw with monotherapy a better disease control rate than they saw in combination.
As you know, Opdualag is a, is currently one of the standards of care first line. With that data, it gave us confidence to go into first line in combination with Nivolumab. Our Phase 3 study, PRISM-MEL, is Nivolumab plus brenetafusp, which is our prime T-cell engager, and compared to Nivo monotherapy or Opdualag.
We're actually, I think, one of the first studies to include Opdualag in the comparator arm because obviously we saw this shift in the standard of care, so that was important to make sure that was included in the trial.
Got it. Then how do you see the opportunity in then the frontline setting?
Frontline setting, TEBE-AM opportunity is up to 4,000 patients. Frontline setting is up to 10,000 patients for brenetafusp. Significant opportunity. I also do think that this is one of the first few different modalities, right? The LAG-3, PD-1 and CTLA-4 are all checkpoint inhibitors. And obviously they work very well, but this is really the one, if positive, could be the one differentiated mechanism of action in this setting.
Got it. How could potentially having both brenetafusp, and KIMMTRAK in cutaneous melanoma, how could that interplay work?
I think we could leverage a lot of synergies from a, you know, whether it's a field force medical team perspective and, you know, certainly costs and distribution. All these aspects I think become synergistic. You know, you could see how we could build a significant cutaneous melanoma franchise, and we would become one of the significant players in cutaneous melanoma, provided all these studies are positive.
I think importantly as well, it's a lot of the insights connect, meaning if you know how to administer KIMMTRAK from a T-cell engagement perspective, CRS management, et cetera, that translates into PRAME as well, right? There's a lot of cross learnings of the platform that could work in our favor.
Got it. How are you thinking about the opportunities beyond melanoma for PR AME?
This is also an exciting year because we have several opportunities reading out at the end of the year. We expect to see signal seeking in lung cancer, so data from lung cancer of our signal seeking study in the second half of this year.
We also expect to see confidence building in ovarian cancer, in this case, in the platinum-sensitive ovarian cancer setting, where we're combining brenetafusp with Avastin. We also expect to see from our PRAME half-life extended some data that all of these together will give us a view on what the future next steps could be for the platform, for the PRAME platform.
Got it. Can you help set expectations for maybe the lung, ovarian, and I think you said the half-life extended updates expected later this year?
Sure. In lung, we said it's signal seeking, and the reason for that is because lung is very heterogeneous. You, you have to do combinations, you have to do, you know If you do lung second-line, second-line lung is a very different disease. In fact, docetaxel is still standard of care, which tells you how aggressive and difficult to treat of a disease it is.
You, you have to go into, you know, EGFR- positive and first-line combinations, et cetera. We're gonna have a comprehensive data set around this different data exploration. Again, we're seeking for a signal. Then in ovarian cancer, we've already published our platinum-refractory ovarian cancer data, and that showed good monotherapy activity as well as good combination activity.
What we're going is in the platinum-sensitive setting because we believe these patients have smaller disease, or we know these patients have smaller disease and higher T-cell fitness. We believe that the platform could potentially do better in that setting. From a preliminary perspective, it's those ascending data.
There we hope to see some potentially confirmation of which is the go-forward dose as well as, you know, data to suggest whether we could leverage our preliminary platform or brenetafusp, which is our short half-life platform. Of course, a short half-life platform has already proven itself with the overall survival data, both from KIMMTRAK and from brenetafusp. You know, this is still a question that we would be looking to ask.
Got it. I think in the past, you guys have spoken about how the speed of enrollment has, you know, you're not seeing the same thing depending on the tumor type that you're testing the drug in. How would you kind of characterize the pace of enrollment for brenetafusp across these different tumor types today?
I think the speed of enrollment has been very good in cutaneous melanoma because a lot of our sites were cutaneous melanoma sites. Eventually, when we expanded into ovarian, that picked up fairly fast and enabled us to enroll very well. Similarly in lung cancer, which were fewer sites in lung cancer, so that took a little bit longer to enroll.
That being said, I think across the board, the reception has been very good, both in terms of this new modality and in terms of PRAME as a target because it's a very highly expressed target across all these diseases.
Got it. What would you say the benefits of a half-life extended version could be? How are you thinking about that today?
When you look at the PRAME HLE, the half-life extended, it's really the same molecule as our brenetafusp molecule. We just add an Fc region for half-life extension. What we're asking is, okay, we know the data with KIMMTRAK with short half-life of 8 hours is still quite exceptional from a 0.5 hazard ratio on OS perspective.
The question is, could you improve either on convenience, obviously by giving it less often, or could you improve potentially on response rate and efficacy through the half-life? I think that's still an open question, but this is a good experiment for us to look for because obviously it's the same molecule just with the FcRn.
It's gonna be very telling once we have these two data sets together.
Got it. Maybe we'll go beyond oncology now. Can you talk about the efforts in terms of the applications of your platform towards, we'll start with infectious diseases?
Another, I think, exciting setting is the HIV functional cure study. When you think about one of the benefits of the platform is, we are able to kill at a much lower expression level. When you think about infectious diseases such as HIV, usually these are dormant viruses. The expression on the cell surface is not very high.
This could be a good fit for our platform to kill, because it kills at this lower expression level. That's what we're testing. We're testing to see whether we can impact the reservoir of HIV and potentially reignite an immune response so that patients can live without drugs for a long time. Currently, we completed our single ascending dose. Now we're in our multiple ascending dose.
We showed data last year at a conference. Based on that data, we have some confidence because we saw a few patients control their disease. We have some confidence to continue to move forward in dose escalation. We are trying to confirm that. If we can confirm that what we saw in those first few patients, that gives us good confidence to move into the next step of HIV development.
Got it. How about for autoimmune disease applications? How are you guys thinking about the applications of your platform?
In autoimmune, I think this platform is very differentiated. Most autoimmune treatments today are systemic treatments, right? And those come with systemic side effects, right? Tolerability issues. We have the first, as far as I know, tissue-specific platform. This is in inhibition or downregulation of the immune system at the tissue-specific level.
Our first exploration is actually in type one diabetes, which is obviously an area of high unmet need. In type one diabetes, the only drug approved today is teplizumab, and that basically is a T-cell depleter, so again, it has systemic implications and issues.
With our platform, what we hope is to coat the beta cells with PD-1 agonism and basically tamp down that immune response and hopefully prevent the incidence of worse disease and save some of the healthy cells.
Got it. What are some of the timelines associated with those efforts?
With the type 1 diabetes, we're looking to get into the clinic, in this first half of the year, and then, you know, data, once we start enrolling patients, we'll communicate more on the timelines for that data.
Got it. How are you guys thinking about business development opportunities for the company?
Today we're pioneers in T-cell receptors. Part of the business development goal is what are the technologies that can enable us to continue to be pioneers in this setting? That's one of the focus points. The second focus point is very much, you know, we're obviously having an excellent footprint so far in oncology.
You know, could we complement some of our exploration in oncology with assets that make sense, right? I mean, we talked about KIMMTRAK being the first T-cell engager in a solid tumor, you know, could we complement in that respect?
Overall, you know, we view business development as, you know, opportunistic in that anything that increases either the return or patient impact, then that's something that we'll take a look at when it makes sense.
Got it. remind us, what is your cash position?
We're actually at around $860 million this year. Interestingly, while we were marginally profitable only two quarters last year, we managed to increase our cash by $40 million over the past year. Obviously, it's not our goal today to be cash flow positive because we have a lot of investment. We're still pioneering this platform, clearly we're in a space where we're very diligent with our investment and our expenses. We expect to continue to be very diligent in this sense.
Got it. What should we be expecting in terms of, you know, profitability, in the future?
We're not guiding to profitability. However, you know, John Goll is our Chief Accounting Officer, he's here in the room with me. He would not allow me to not say that at some point we'd like to be profitable. I think that point comes with us investing in a, you know, diligent, data-driven way into our pipeline because I think that's what maximizes shareholder value is, you know, good investments. We'll continue to make good investments.
Understood. Let me check to see if there are any questions in the audience. All right. Maybe just last question for you. Can you tell us what the key catalyst and milestones are for the company for 2026?
Today, we continue to execute on uveal melanoma and KIMMTRAK. We expect incremental growth in 2026. We expect also the KIMMTRAK lifecycle management KIMMTRAK study, which is up to 4,000 additional patients. That is finishing enrollment in the first half of the year and data as early as the second half of the year for that Phase 3 lifecycle management program.
We also expect brenetafusp readout in both lung cancer and ovarian cancer at the end of the year, as well as dose escalation data from our PRAME HLE program at the end of the year. Based on the totality of that data, we'll make some informed decisions as to next steps.
Last but not least, we expect the HIV program to read out as well, more data towards the end of this year. That will also enable us to tell whether, you know, what's the next step from an HIV perspective. A data-rich year, I think, for us, coming from a 2025 execution year.
Yes. Excellent. We're looking forward to it. Thank you very much for taking the time.
Awesome. Thank you so much for having us.