Okay, I think that's our signal to start. Good afternoon, everyone. Welcome back to day two of the Cantor Healthcare Conference. My name is Eric Schmidt, and I'm joined by my colleague, Imogen Mansfield, and it's our delightful pleasure to welcome our next presenting company, Immunocore, one of our favorite stocks to be acquired right here, right now. Thrilled to have with us the company's Chief Financial Officer, Travis Coy, and also Mohammed Dar, who is EVP of Clinical Development and the company's CMO. Travis, Mohammed, thank you for being here. I think let's start at a high level. For those a little less familiar with the story, Travis, maybe you can give us the state of affairs of the company.
Happy to. Eric, Imogen, thank you for having us. We appreciate it. Happy to be here. Immunocore is a commercial-stage biotech company. We have a clinically validated T-cell receptor platform that we pioneered with the first-ever approved TCR therapy in KIMMTRAK. KIMMTRAK is indicated for HLA-A*02:01-positive frontline metastatic uveal melanoma, generated about $220 million of revenue in the first half of 2026, and has become the established standard of care in that indication across all major markets. Beyond KIMMTRAK, we have three ongoing phase III studies in various melanoma indications. Two of those phase III studies are lifecycle management plays for KIMMTRAK, and then the third phase III study is for our PRAME-targeted bispecific called brenetafusp. Of the two phase III lifecycle management plays for KIMMTRAK, the first one is referred to as TEBE-AM in advanced cutaneous melanoma.
Enrollment is nearly complete for that study, and we expect to have a top-line readout on an overall survival endpoint as early as the end of this year. The second lifecycle management phase III for KIMMTRAK is in adjuvant uveal melanoma. It's referred to as the ATOM study. Enrollment is earlier days in that study, and hopefully we can have enrollment completed sometime in 2028. The third phase III that I referenced, beyond KIMMTRAK, is with the PRAME-targeted agent called brenetafusp, called PRISM-MEL-301, and that is in frontline cutaneous melanoma. Enrollment is progressing well in that program, and hopefully will complete by the end of 2027.
Beyond the three phase III studies, we have an earlier-stage oncology pipeline that includes studies with brenetafusp and a half life extended version of brenetafusp in ovarian, lung, and melanoma, and we hope to have data for those programs to disclose later this year. Beyond oncology, we have some efforts in infectious disease and autoimmune with our first foray in the clinic with our type 1 diabetes program that should have the first patient dosed any day now, so very soon. A little bit just on the financial side, we have a very robust balance sheet with $880 million of cash that will fund, along with the revenues from KIMMTRAK, have the ability to fund the pipeline and the company for the foreseeable future.
Maybe sticking with the financial outlook, Travis, you've kind of been bumping up around profitability several of the last quarters, or break even, I would say.
Yeah.
But when you think about allocation of the resources you do have and the revenue stream, how do you think about reallocation into the pipeline or into non-oncology programs or even into a return to profit for shareholders?
Yep. Yeah. No, thanks, Eric. So three key things from a capital allocation perspective. First, making sure we maximize the value of KIMMTRAK, both with the current commercial indication in uveal melanoma, as well as with the potential for upcoming cutaneous melanoma, assuming positive data from TEBE-AM. The second is advancing the three phase III programs, and obviously getting those to data readouts. And then the third is funding the earlier- stage pipeline and the platform. We don't want to be complacent with the platform either and continue to make investments in that as well. From a profitability perspective, a little too early to comment on profitability. You touched upon it. We've had some quarters where we've been slightly profitable and other quarters where we're not quite profitable, so we're at about a break-even state.
That profitability, we want to make sure we're investing today and creating value for the long term, so a little too early to guide on any profitability, yeah.
And we will get deep into all the programs.
Yeah.
What do you think investors are missing about the story?
From my perspective, we have a product generating over $400 million of revenue. We have three ongoing phase III trials that have the ability in these next two to three years of all providing data readouts. I mentioned the earliest is TEBE-AM, with one as being as early as potentially the end of this year. Beyond that, particularly with the type 1 diabetes, getting the first dose in the type 1 diabetes patient, I think in immunology, if we are able to show successful tissue-specific down modulation of the immune system, that has the ability to unlock a lot of value. So with a revenue stream that is largely funding the company and with several opportunities for data inflection, particularly over the next two to three years, I think that creates a very attractive profile for us.
Okay. Let us touch at least upon KIMMTRAK and the commercial opportunity. This drug continues to grind higher, grow and grow and grow, I think beyond anyone's initial expectations. What is the driver?
Good commercial execution and a high amenity. Before KIMMTRAK, uveal melanoma was a historically very immunologically cold tumor. It really had no standard of care and hadn't had, I think, an advancement in almost 40 years at the time. To be able to show a very durable survival benefit that we've shown with KIMMTRAK, we recently had five-year overall survival data that showed a doubling of survival, which we're obviously very pleased to see and quite remarkable for these patients. We have some patients that have been on therapy now even five, six, seven years, which was unheard of really prior to KIMMTRAK. These patients just didn't have a good outlook. That alongside, like I said, good commercial execution, has led us to become standard of care across all major regions. And we're upwards of 70+ percent now penetrated across both the U.S. and Europe.
We've also seen a duration of therapy that is unique, and it's worth mentioning, of about 14 months in the real-world setting, and that has gone beyond what we actually saw in the clinical setting. And that's nearly unheard of in oncology. Usually, you see some deterioration of that duration of therapy as you get into the real world, and I think that just speaks to the attractiveness of the product profile that KIMMTRAK brings to these patients.
In the coming year, you may have your first competitor in the uveal melanoma setting. What do you make of that?
We anchor on our value proposition that has got us to be the standard of care in all those major markets that I referenced. It's based on a very durable survival benefit, again, that has been reinforced with that five-year overall survival benefit. It's also based on that safety profile that I mentioned that is predictable and manageable and doesn't have any cumulative toxicity. One of our growth opportunities that we continue to focus on in the U.S. is getting into that community setting. We now have about 70% of our starts in the community setting, and I personally don't think we would've been successful in doing that if it wasn't for the strong overall survival benefit and that safety and tolerability profile that KIMMTRAK provides.
Some investors are worried you're going to see a down year in sales. Is that within your scope of probability?
I don't think so. We've continued to see growth. Yes, growth is moderating. I mentioned 70% penetration across all major markets. Given that we are the fifth year on the market, that growth has moderated, but growth should be moderating given that we're the fifth year on the market, right? I think we've been successful in that commercial execution. We don't take, obviously, any competitors lightly, and we'll continue to monitor the data that emerges, and think we have a very attractive value proposition to compete.
In terms of the offensive opportunity in uveal melanoma, you mentioned the ATOM study into an adjuvant setting. Maybe you could just give us a little bit more on that trial, the timelines, and the probabilities of success.
You want to touch on that?
Sure. Eric, I am happy to comment on it. Just at a high level, the ATOM study, as you alluded to, is an adjuvant trial. It is based on the fact that we had very promising survival benefit in the frontline metastatic setting. While all patients benefited, what we noticed was that the survival benefit and even the PFS benefit was even greater for patients with smaller tumors, supporting the idea of going even into this earlier line setting where there is actually currently no accepted standards after patients undergo primary therapies, essentially wait and worry for the tumor to come back. This is a trial that is being run by the EORTC, which is one of the largest cooperative groups in Europe, have a lot of years of experience running adjuvant trials, especially in melanoma. The trial started about a year and a half ago with startup in Europe.
This year, we announced that sites expanded to U.S. So we have had site open up in Europe, and the plan is continuing to ramp up site activation. In terms of timelines, we expect, based on what we know right now, that the enrollment should be able to be completed by the end of 2028. The primary endpoint is a relapse-free survival, which is an event-based endpoint, which would come sometime after enrollment is complete.
Standard of care is, or the control arm is watch and wait.
Observation.
Yeah. What would you expect to be a timeline of events in observation?
What this trial is enrolling is the group of patients who have high risk for metastatic disease occurring. That's somewhere around 40%-50% of patients who are newly diagnosed. In that high-risk group, the median time to relapse is somewhere between two and three years.
Thank you. Want to go with TEBE-AM ?
I guess just one more on this. You've talked about the potential to reduce the overnight stay for the first few doses of KIMMTRAK. How is that going, and how much do you think that that could expand the opportunity in the metastatic uveal melanoma setting in the community?
I can start, and maybe Travis can add. The approach that you have to do since the current label requires the overnight observation is you need to generate prospective data to show that you can reduce that overnight monitoring without making the safety profile worse. That's what you need to do in order to change practice. We're working on generating prospective data, but in terms of our approach across the platform, we've already embedded trying to adaptively reduce monitoring on the PRISM-MEL-301 study, which is one of our ongoing pivotal trials. The goal is for all future programs to not be requiring overnight monitoring if it's not required.
TEBE-AM.
Please.
Okay. Remind us of the phase II/III design here for the TEBE-AM study. You have already mentioned that enrollment is ongoing, but any more guidance you want to provide there on when you think that might complete?
Sure. Just as a reminder, the TEBE-AM trial is, as you said, a phase II/III trial in second-line plus cutaneous melanoma after failure of checkpoints, as well as if you are BRAF mutant, BRAF-directed therapy. The trial is a three-arm trial. It is randomizing patients either to KIMMTRAK monotherapy or KIMMTRAK in combination with [pembrolizumab]. The control arm is unique, reflecting the fact there is really no accepted standard. Basically, investigators can put patients on whatever is the accepted local standard. The primary endpoint is survival, which is an event, of course, driven endpoint. Enrollment, yeah, it is nearly complete. We are almost over the finish line, and in terms of headline data, Travis mentioned we think it could read out as early as at the end of this year.
Will you announce when enrollment is complete?
We will. The primary endpoint is event-driven.
Survival. Yes. So how do you think about the decision to take or not take an interim look at that data, an interim analysis? Will you be communicating with investors if you decide not to do an interim analysis?
Sure. Happy to address that question, Imogen. There's been a lot of interest about interim analyses in the TEBE-AM trial. What I'll say, in general, is that in typical phase III trials like this, it's very common to have planned interim analysis. The main reason to do this is to try to get a readout much earlier than the final planned analysis. The other is it's routine usually not to conduct analyses while enrollment's ongoing to avoid biasing patient selection. Then the third is that, depending on when enrollment completes, it's entirely plausible that the time savings that you were originally planning from the interim are now almost negligible, and it might make more sense to not spend [inaudible] on something that you might be only saving, let's say, a month or two.
I think that's really the best way to think about TEBE-AM with enrollment nearly completing and headline data as early as the end of this year.
I'll follow on to just one more. From an investor disclosure perspective, I'd expect to see completion of enrollment, as we just mentioned, and then the top-line readout.
Has the enrollment slowed down at all? I guess there was initially some guidance for it to be a little bit earlier than now. Obviously, a few months for us is a big deal, but in the grand scheme of things, it is not.
Yeah, no, from my experience, the trial's target recruitment is 540 patients. The trial has been open for three and a half years, so it is not uncommon to have enrollment slip by six or seven weeks. We are literally approaching the finish line.
Okay.
In terms of your visibility on that event rate that is needed to trigger the final analysis, where do you stand on that?
It is pretty standard, at least for this trial, we have an independent stats committee that is able to look at the event rate and then just inform us from a planning perspective when they think the analysis could occur. Based on the most recent sort of update, we still are on track for that we could have headline data as early as the end of the year. The other thing we have said is that perhaps by Q3, when we provide our next business update, we can further tighten that window in terms of when we expect to have the final readout.
What can you tell us about the makeup of the control arm in terms of therapies that patients are on?
Sure. I mentioned before that the setting in which TEBE-AM is enrolling patients, there's after failure of checkpoints and targeted therapy. There really is no accepted standard. Even with approval of recent therapies, the survival endpoint really hasn't moved. With regards to the control arm, the original assumptions still hold with recent review, our review of real-world data for both Europe and U.S., which is as follows, that we expect in the control arm about a third of the patients would just essentially get retreated with checkpoint, reflecting, again, really no viable alternative. Somewhere between 20%-25% would get retreated with a BRAF-based regimen, and then shockingly, up to 40% of patients get treated with chemotherapy, get put on a clinical trial, or even just get supportive care.
Our assumptions from three and a half years ago are still holding based on real-world data that we've looked at recently. [inaudible] When you look at those three groups, the way I describe them based on those percentages, the assumption is the blended survival for this type of population that's failed PD-1 has been exposed to CTLA-4 and if they're BRAF- mutant, also BRAF therapy, is somewhere between 10 and 11 months.
You've talked before about doing some analysis between the patients that are on checkpoint retreatment and comparing those to patients who are on the combination in the tebentafusp plus pembrolizumab arm. Will we be seeing that with the top-line data?
It's pretty typical that we don't get into that level of subgroup analyses or details with the top-line data, but it's fairly standard when we would present the data at a scientific congress that you could expect that these are pre-specified subgroup analyses that we would share publicly.
Go.
Yeah, sure. So what have you talked about in terms of study power here? Also in terms of event tracking, are you regularly getting updates on the number of events? How frequently does that information on a blinded basis come through?
Sure. So with regards to power for TEBE-AM, we haven't got into the specifics of the stats analysis plan, but what we've guided to is that it's pretty common for phase III pivotal trials like this, that we are not aiming just for stat sig results. We really want clinically meaningful results, and that typically means at least a 25%- 30% improvement relative to control. With regards to visibility into event rates, as I mentioned before, there's an independent stats group that is regularly reviewing event rates and provides that on some type of regular cadence. Now that we're getting close to what we think is a readout for the headline data, we'll continue to get that type of update from the blinded stats group.
In terms of the performance of the different arms, if we see that the combination arm is successful and the monotherapy is not, I guess maybe you can also speak to the statistical plan there of will you be testing the combo versus the control arm first? In the setting where that does occur, what happens in terms of regulatory discussions?
Sure. A couple points. One, obviously when we designed the trial and discussed it with health authorities, obviously this possibility came up and was discussed. The way the trial is designed, since there's at least two experimental arms, that when the analysis is done, there would likely have to be a hierarchical approach. While we haven't gotten into the details, it would be reasonable to expect that we would prioritize the combo over the monotherapy since most of the phase II date was combination. Assuming that that's successful, even if the monotherapy was not successful or hadn't matured yet, it's very acceptable from a health authority perspective for them to get access to that data and to be using that data to at least assess contribution of components and still have an acceptable overall package to approve for the combination.
Mohammed, with the hierarchical approach you're first testing, we assume the combination arm and then comparing that to the control arm. How do you ensure that there are enough events in those two arms to be able to do the investigation?
Yeah, that's a great question, Eric. When we were referring to that regular update that we get, that update is not for three arms, it's for two arms. It's the two arms that would've been prioritized.
Thank you.
You included patients who had or had prior PD-1 and CTLA-4. What are your expectations there around a label? Have you had any discussions with the FDA around that? Would you be able to include patients that hadn't been pretreated with both of those therapies?
It's a very relevant question, Imogen. What I would say is that ultimately it'll depend on the data, the strength of the data, and this is something that would be part of the discussions we would have with health authorities at the time we have the data available. We wouldn't want to speculate at this point.
Where do you see tebentafusp fitting in in cutaneous melanoma in the second-line setting now with RP1 available, TILs, PRAME cell therapy on the horizon?
Yeah. No, that's a great question. From our perspective, if TEBE-AM is positive, this would be the first trial to demonstrate a survival benefit in this late- line setting. The two agents that you mentioned both got accelerated approval on response rate in the other randomized trial that's close to reading out the primary endpoint is PFS. So that's one key differentiation. Another differentiation of course is just the profile for KIMMTRAK is something that's off the shelf. It's IV. Most of the toxicity, as you heard from Travis, is in the first couple of weeks. There's no cumulative toxicity and the other advantage is that half the patients with cutaneous melanoma are treated by physicians who also treat uveal melanoma. So there's familiarity with KIMMTRAK given the fact it's been on the market for five years.
I just realized we didn't really ask you for your conviction or reasons for optimism this trial will work.
For TEBE-AM?
Yes.
Of course, there's several reasons to believe that motivated us to launch the TEBE-AM trial. The first one is that KIMMTRAK is already clinically validated in uveal melanoma on a survival endpoint. And uveal melanoma, as many people know, is a cold tumor that has low mutational burden and does not really respond well to checkpoints. So that's proof point number one. Proof point two is that the target for KIMMTRAK is also highly expressed in cutaneous, and cutaneous is, unlike uveal, is a warm or hot tumor with mutational burden, which is very sensitive to the IO mechanism. And the third point is that we had this collaboration with AstraZeneca with this phase II trial in cutaneous melanoma with combinations of checkpoints and we saw very promising survival data with one year landmark and median OS looking much better than the historical benchmark.
Thanks.
It's published in JCO in 2022 or 2023.
Can we talk about PRAME?
Well, maybe just a quick view on how you size up this opportunity. I think you've given some patient numbers.
Yeah. I'll happily take that. I'll speak to actually both lifecycle management plays across TEBE-AM and ATOM. With respect to TEBE-AM specifically, with the current uveal melanoma indication, we're at about 1,000 eligible patients. TEBE-AM could provide us access up to an additional 4,000 patients, and then the ATOM study could provide us up to additional another 1,000 patients from a lifecycle management perspective.
Thank you.
Okay, the PRISM-MEL-301 study. We do not get that many questions on this one because it is a little bit further away. What makes you optimistic about the success for your PRAME- bispecific in frontline melanoma in the phase III study?
Yeah. We are quite excited about brenetafusp PRAME-targeted TCR bispecific for a couple of reasons for cutaneous melanoma. One, we showed two years ago and recently provided an update at ASCO a few months ago that we see monotherapy activity in late-line cutaneous melanoma patients that are even primary resistant to checkpoints have progressed within six months of starting, as well as patients who have poor prognosis brain mets, liver mets. We see clear activity. Recently what we showed was the dose that has been selected in PRISM-MEL-301 by the IDMC to go move forward. We saw a 17% monotherapy response rate in this late-line population with a median OS of about 14 months, which is on par with adoptive cell therapy, TIL therapy.
That is one really strong piece of data that was not demonstrated for LAG-3, let us say, for example, that is now well established as a standard of care. Never showed monotherapy activity. The other is we can safely combine with checkpoint and showed promising data at ASCO this June in refractory melanoma. The third is the fact that this mechanism is distinct from checkpoints. You would expect that if you combine two agents that have monotherapy activity that work in a distinct manner, that at least you should see additive activity. We have data from our platform in uveal that when we move from late-line to earlier line, that we see better activity. Those are the reasons that gave us confidence to move forward with the PRISM-MEL-301 study with brenetafusp.
Remind us of the phase III study design and the timing for when we may see data.
Sure. The PRISM-MEL-301 study is a randomized phase III trial where the experimental arm is the brenetafusp TCR bispecific in combination with nivolumab, compared to a control of either nivolumab or Opdualag. The choice is based on country-level approval for all-comer. If there is all-comer approval, regardless of PD-L1 status for Opdualag, it is the control. Otherwise, it is nivolumab. The primary endpoint is PFS, which is event-driven. We last year accrued 90 patients and had the IDMC take a look, and they selected the top dose to go forward. At this point, we are on track because we have activated the full complement of our trials, 200+ sites globally. We think fairly confidently that we think we can complete enrollment by the end of next year. The event-driven endpoint typically is 6- 10 months after enrollment is complete.
You also have an HLE PRAME program with data coming later this year. Do you think that a longer half-life makes a difference?
That is the exact question we want to ask, and we have designed the right experiment. We have over 400 patients in our phase I trial treated with our non-half-life extended. This very similar site footprint and similar tumor type enrollments going on with essentially the non-half-life extended with the Fc, which is the half-life extended molecule. That is how we have designed the experiment, and we are happy with how enrollment is going. Once we have the full data and we can tell a story, we are looking forward to sharing the data.
If it looks good, which indications will you pursue if it, for example, if it looks better than brenetafusp?
Sure. The way we're thinking about this is that we obviously have maturing data that we've indicated that we look forward to sharing in ovarian and lung from brenetafusp, the study that's been open much longer. We're accruing similar tumor types with the half-life extended. The goal would be is that we would want to compare across both the brenetafusp data set as well as the half-life extended to guide what the next steps would be in those additional tumor types.
Would you do a half-life extended KIMMTRAK?
Sorry?
Would you do a half-life extended tebentafusp?
Oh, will we have half-life extended tebentafusp? It's something that we're thinking about. It's certainly a possibility.
I guess one last program to touch on, PIWIL1. Could you tell us there about the kind of data that we're going to see here and what gives you optimism for this target in CRC?
Sure. PIWIL1 is really exciting target and also shows sort of the strength of the platform. It's an intracellular target, belongs to the cancer/testis antigen family. As far as we know, this is the first clinical program that's targeting this protein, which is overexpressed in mostly GI cancers, especially colorectal including MSS colorectal. The phase I trial opened last year, so we've been in the clinic for about a year and a half. Dose escalation continues, and what we're hoping to do is share data from the phase I experience likely sometime next year. It's predominantly colorectal patients, and the typical data would be safety and, of course, early efficacy from late-line refractory colorectal patients.
Great. I think that's all we have time for today. Thank you so much, Travis.
Thanks, Travis.
Thanks for joining us.
Thank you for having us.
Thank you.