Thank you so much. My name is Peter Lawson. I'm one of the biotech analysts at Barclays. I cover some mid-cap oncology names predominantly. Many of my names kind of make an interesting pivot as well. I am really pleased to have with us Immunocore. We have the CFO, Travis Coy, and Ralph Torbay, Head of Commercial. A series of questions I have been asking at companies just at the kind of macro level: how you look at supply chain, especially in the light of tariffs, and if there is any long-term or near-term, short-term impacts on the supply chain that we should be thinking about.
Yeah. I think for us specifically, obviously, we're in a great position from a company perspective. At least to date, we have not seen any disruptions. That being said, we do manufacture KIMMTRAK in Europe. We have to continue to make sure we closely monitor the situation. There has been talk about tariffs from Europe. We have to continue to monitor that situation because we're cognizant that there could be an impact potentially to the cost of goods sold . No impact to date, no disruptions to date, but still staying close to, obviously, the macro environment and what's going on from a tariffs perspective.
How do you kind of hedge against that on the COGS side of things? Is there a way of doing it, or?
Yeah. It depends. Probably too early days yet to talk about specific remediations that we may be able to make to help mitigate any downside that could potentially come from that. We're also a bit unique in that our platform has such strong potency. KIMMTRAK, for example, is 68 mcg. Our gross margins are just over 99%, which is unique for a biotech, particularly one of our size, to be able to have gross margins at that level. We do look at things, and we're making sure we're planning with various scenarios that may or may not happen, and we'll sort of act accordingly.
Gotcha. Thank you. The other macro question I've been asking just around the FDA, kind of potential cuts there. Have you seen or heard any kind of slowdown in communication, and how's that communication been for you?
Yeah. There is a lot of changes going on in the system, which is obviously, I think, leading to some unpredictability for a lot of people. But thus far, we have not seen any changes in speed or responses or any of those elements in the reaction with the FDA. We'll continue to work with them and make sure we implement things as quickly as possible and continue to stay up on top of changes that occur there. But thus far, no impact thus far.
Yeah. Any worries around these potential restrictions around biological manufacturing partnerships or these cross-border licensing agreements? Is there anything there we should be thinking through?
Yeah. For us specifically as a company, we do not expect any impact. What I will say is just from the broader biotech ecosystem, we are going to be supportive of making sure we can access innovation wherever it is. I think that is something we need to, obviously, not just as Immunocore, but again, as a biotech and pharma ecosystem, make sure we are cognizant of and hope that that continues to be the case, particularly speaking to your cross-licensing question.
Perfect. Thank you. I guess final kind of macro question just around NIH budgets being cut. Is there any kind of thing near-term, mid-term that we should be kind of thinking about, even if it trickles through to, say, clinical trial sites and universities?
Yeah. Actually, similar to tariffs, we haven't seen an impact to date. We want to make sure, obviously, the NIH plays an incredibly important role in the ecosystem. They, in many instances, are the source of a lot of the innovation in the United States and more broadly. We definitely want to keep an eye on that in some respects. We've had some instances where we've approached people for positions that are good scientists. It may provide an avenue there to actually bring some of those people over into industry.
Gotcha. Perfect. Thank you. Just back to your data, the great data today with HIV. Kind of how do you look at that data, and how does it kind of inform how you're thinking about moving forward?
Yeah. Really encouraged by the HIV data that we had a chance to disclose at the CROI Conference yesterday. Just to orient everyone, this was initial multiple ascending dose data of 16 patients with three different dose cohorts. As Peter is alluding to, we're actually really encouraged by the data. We are looking at two key things that you're looking at in the phase I trial: safety and efficacy. From the safety perspective, given our platform and that that therapy has a CD3 arm, making sure that CRS was manageable. Very pleased to see that the CRS that we did see in the highest dose cohort was upon the first dose, and it was resolved, and it was a low-grade one fever and resolved within four hours of occurrence. The other aspect is then efficacy. Really pleased.
Keep in mind that this therapy's intention is for a functional cure of HIV, something we have not seen in the industry to date. I am really pleased to begin to see with dose escalation some reduction in the viral reservoir in some doses and also some viral control at the higher doses, which means we are delaying rebound from patients coming off of antiretroviral therapy. Obviously early days, but seeing evidence in sort of those three patients. We saw one evidence of that in the 120-milligram cohort and then two patients in the 300-milligram cohort. That gives us the confidence to continue that dose escalation that you are alluding to. That is what we intend to do.
Yeah. Where are you for dose escalation?
We actually just started. We finished the data that got disclosed yesterday at CROI was from, as I mentioned, the dose escalation up to 300 micrograms. Because of the safety profile that we're seeing, we've now amended the protocol of the trial to go even higher. We're just beginning. That took a little bit of time to do. We're just now beginning the dose escalation. Hopefully, we'll have data from that dose escalation in the next 12 months- 18 months.
Okay. So you think it's 12 months-18 months before we see the next cut of data or just the patient?
Probably so. That's our best estimate at this time. Like I said, we just started it. Keep in mind that the trial is designed such that it's 12 weeks of our therapy combined with ART, so antiretroviral therapy. It is another 12 weeks of monitoring to see that viral rebound and see if there was a delay in that viral rebound. That is already 24 weeks. That is what I say. By the time we do enrollment, have that monitoring period, we're probably looking at about 12-18 months at this point in time.
Gotcha. Thank you. Longer term, where do you kind of want or where do you think it could potentially get to for a sense of viral reservoir reduction and lack of rebound? What's kind of the right number or the position?
Yeah. Sort of what is the target product profile, if you will? Yeah. As I mentioned, the objective is a functional cure. When you talk to KOLs, and there was actually a recent paper just published on this that sort of said the baseline of what we're looking we'd like to be able to achieve is delaying ART, so delaying reinitiating ART, antiretroviral therapy, for about two years. That's sort of what we're hoping to achieve. We have some work to do. Again, this was early initial multiple ascending dose data. We are encouraged the fact that one of the first therapies to ever show a delay in that rebound and a reduction in virus in the reservoir as well gives us good reasons to believe. Hence why we're continuing to escalate, dose escalate.
Gotcha. Thank you. I guess the read-through that we should have or you would think from the HIV over the HBV studies?
Yeah. Certainly some similarities and some differences. If you think about HIV and HBV, similarities being both similar constructs from a platform perspective in that we're taking a bispecific and using the CD3 arm to engage T cells to bring those to help fight the virus. That part's similar. In the case of HIV, I mentioned we're targeting the GAG protein expression. In the case of HBV, we're looking at a different protein expression called envelope. Similarities of what we'll be looking for, Peter's alluding to the fact that we're disclosing our single ascending dose for HBV in the second half of this year. Things we'll be looking for that are similar to HIV will be, were we able to see a dose-dependent response in cytokines? That tells us that we're getting T cell engagement and that those T cells are being brought into HBV.
Ultimately, we'd like to see some evidence of HB surface antigen reduction. Hopefully, we'll be able to provide some of that data, or we will provide some of that data in the second half of this year.
Gotcha. Thank you. Are there similarities or things you've learned from the HIV program that we've seen that kind of help inform HBV and whether it's dosing or safety profiles?
Yeah. One of the things with HBV, people that have HBV in particular, they are a typically well-controlled patient population. I think that's one thing you need to keep in mind. The other end, very honestly, that has led to some more challenges in enrolling that study than we had anticipated. The other thing we're also looking at from the HBV that I could highlight from a differences perspective is because they're so well-controlled and because of the way the mechanism of action works, we are also looking at whether there's some productive transaminitis, meaning we expect to see some ALT and AST increases because of that mechanism of action. Therefore, we want to make sure we have to thread a little bit of the needles. We want to make sure we don't cause any liver tox.
That's also one of the reasons we've been more cautious with that program. That's one of the needles we're ultimately looking to thread as we potentially move forward.
Okay. What's the process of threading that needle? What do you have to do? Lower doses?
It's really a balance of safety and efficacy. Yeah. That's what the single ascending dose trial is, just kind of the beginning of that journey.
Okay. How many patients should we expect to see?
We haven't disclosed the exact number of patients. If you think about a sort of typical phase I single ascending dose study, usually you're looking at mid-teens in that range.
Okay. Is there kind of an internal or external goal around the BAFSA success , whether it's irAEs increases or what are the metrics we should be looking at?
Yeah. I mean, ultimately, safety, as I mentioned, because that construct is the same CD3. The bispecific has that same CD3 arm that I mentioned. We need to look at CRS and safety and make sure that is manageable. I mentioned the transaminitis as well. Again, going back to really want to see some reductions in that HB surface antigen and using that data as the determination for next steps.
Keep in mind it's a single dose, right, of the drug, so.
Yeah. Versus, as Ralph points out, that's obviously different than the multiple ascending dose data that we disclosed yesterday.
That's a good point. Yeah. Okay. What do you need to start that multiple ascending dose in HBV?
I'd actually tie it back to exactly what I said, is that safety and reduction of surface antigen. Those are the two things that we're really looking at.
Remind me, in the HIV population, did you see that AST, ALT elevation?
Yeah.
This is specific to.
It's specific to HBV and the biology of both the disease.
Some cause, yeah.
Yeah. Both the disease and the mechanism of action that we have.
You're killing hepatocytes, so you expect changes in the.
Yeah. Yeah. Good point.
Is there a way to mitigate that? I guess not. I mean, that's what you expect. That's the mechanism of action. The question Travis was saying is you want to make sure that it's the unhealthy ones or the infected ones that you're killing, not the healthy ones.
Yes.
Okay. The CRS you saw, it was minimal. It resolved very quickly. I mean, as you escalate, it's presumably going to get worse, or do you think it just extends in time, or do you think it goes from grade I to grade II?
Yeah. It is part of what we will continue to explore with the dose escalation. We are back to HIV. Part of what we will explore as we continue to dose escalate. We have a lot of insight from the oncology data that is generated both clinically and preclinically that we have applied and will continue to apply to that dose escalation in the HIV program. Very encouraged by, again, only seeing grade one CRS so far at the highest dose. Also, other thing to remember is we do a step-up dose to get to that target dose. We will be looking at how to optimize that as well to minimize that CRS.
Okay. Perfect. I'd love to pivot a bit just for the launch and the very successful launch you've had. Kind of what are the drivers left we should be thinking about in the growth opportunities for KIMMTRAK?
Peter, we've been doing very well with KIMMTRAK, establishing it as a center of care across most major markets with over 80% share of HLA-A*2:01 patients. Last year alone, we delivered $310 million in revenue, and that was a 30% year-over-year growth. To your question, I still think there are areas of opportunity. Number one is in the U.S. We still are going after the community where there's still some penetration to be had. The good news is that we have half of the patients already starting in the community.
About two out of three patients are being treated in the community, which speaks to the well-tolerated profile of the medicine and the efficacy. There is opportunity also in the duration of therapy. We are seeing something that for me is unprecedented where you see the duration of therapy in the real world doing better than the duration of therapy in the clinical trials. That speaks to patients doing well. Lastly, we are prosecuting a few launches outside of the United States. There are still some countries remaining. Most recently, we launched in the U.K. and Poland. There are still a few countries where we are working on reimbursement in Europe. That is, I think, the next incremental phase of growth.
Gotcha. Thank you.
Maybe digging into some of those duration of therapy, do you seem to expect that's going to continue beyond what, 11 months or so that it is now?
I'm hoping so, right? Because a patient that's on therapy is a patient that's surviving and doing well and with controlled disease. I think what we're seeing in the real world is we don't have a good guidepost from the clinical data because it's extended beyond the clinical data. We're all learning together. Yeah. Do you think a similar dynamic happens in ex-U.S. as well? I don't know if that's a U.S.-driven event where you're getting beyond 11 months or if it's kind of a global event.
Interestingly, it's more pronounced in some countries outside of the U.S.. What we're seeing is that physicians who are able to find patients earlier in their disease course as well as physicians who basically are very well-educated on treatment beyond progression tend to have patients that do better and stay on for longer. In Europe, it's a more centralized healthcare system, and therefore you see a little bit more of those sort of experts being able to treat patients a little bit longer.
Interesting. Okay. Then the new countries we should expect to see in 2025?
We recently announced that we have an approval in Brazil. We expect inpatient access there. We submitted for reimbursement across several other European countries that we're still working to get reimbursement. You can expect some of those to come online this year. Last year, we had 14 launches, 24 countries in total. We're working on a few other launches this year. It's all incremental to the U.S., I would say, though.
Great. Are there particular geographies that are coming online that could move the needle, or these are kind of diminishing returns? How should we think about those additional geographies?
Yeah. I think it's incremental in the sense that the U.K. is probably the largest country that we're launching in the first quarter. Poland is actually large as well. And then there's a few other countries like the Netherlands, for instance, where we don't yet have reimbursement and the final stages of that conversation.
Gotcha.
Peter, if you think about the growth that we saw in 2024, we had 30% year-on-year growth, right? What led to that was quarterly sequential growth of a range of about 5%-7%. Naturally, in any product's lifecycle, you begin to see that growth moderate, and that's what we're expecting. We are expecting that growth to moderate from those kind of quarterly sequential levels that I mentioned. We do continue to expect growth, as Ralph was articulating.
Gotcha. Okay. How do you think about emerging competition in the space? I guess the IDEAYA is the obvious one. I know I'm not going off to the same page as you, but how do you kind of ring-fence the existing business, or if that's the appropriate way to think about it?
First of all, I think that we're awaiting their phase III results, of course, which, if positive, would be good news for HLA-A*2:01 negative patients. For the positives, really, KIMMTRAK is a center of care across major markets. We have established three-year overall survival. Really, the benchmark is patients are surviving. Physicians are seeing in the real world their patients surviving, as we discussed about duration of therapy. I do expect KIMMTRAK to remain the center of care worldwide for HLA-A*2:01 positive patients.
Gotcha. How should we think about or how worried should we be about off-label use when it is actually used in HBV-positive population?
There are two geographies, right? The US, where off-label use is more common. There, I think it's about, again, that value proposition for the patient. As a patient, I want the chance of survival. That's the most important endpoint for patients. I think in the context of that, physicians will have to make a decision of what to use first. So far, again, KIMMTRAK is a center of care. In Europe, for the most part, off-label is not a common fact. I think that there it's not even an issue.
Gotcha.
Peter, the one thing I'll tie into Ralph obviously mentioned overall survival, which is clearly important. The other thing is tying back to his comments on how we've seen the duration of therapy go beyond the clinical trial setting is the safety profile. That is something we've been incredibly encouraged by, hence why we're seeing the starts that we're seeing in the community and why our growth is expected to come from the community in the U.S. going forward is they're getting comfortable with that safety profile, which is absolutely terrific to see.
Okay. Thank you. Maybe in the last few minutes, if we pivot to PRAME, what should we think about potentially falling in 2025 versus 2026, if it is the ovarian data, mono combo arms, or the lung data, how that falls this year, next year?
We have had very interesting single-agent data and combination in the platinum refractory setting in ovarian cancer. The single-mono therapy data, sorry, was we saw disease control rates of around 60%. The combination, we saw that around 70% and like 23% overall response rate. Really very interesting data, and we are building on that signal in two ways. One was we are expanding our cohorts in combination with chemotherapy in the platinum refractory setting, and then we are also going into the platinum-sensitive setting to explore combinations with bevacizumab and other therapies as well. In lung cancer, we are building upon the signal that we have seen. Sorry. In lung cancer, we are signal searching. While in ovarian cancer, we are building upon the signal.
In lung cancer, we're signal searching, and that means that we're going into combinations in earlier lines and looking for lung cancer is a fragmented space, so we have to look at segment by segment.
Is there update? There should be updated data in ovarian this year, or is it next year, or?
We are currently enrolling patients, so we expect in 12 months- 18 months, as data comes, we will share. We do tend to share data at conferences because we think peer-reviewed data is very important.
Okay. How big a data set will that be in lung cancer? How many patients?
Yeah. Honestly, it depends on the data, Peter. It depends on the data, and where that data takes us will ultimately determine how many patients we continue to expand in those cohorts.
Okay. Oh, and then in ovarian, where does that eventually fall? Is that kind of second line, third line? What line of therapy for ovarian, do you think?
In the platinum-sensitive setting, it's probably second line plus. In the platinum refractory setting, it's third line plus. Yeah. Peter, I'd be remiss if I don't mention the fact that TEBE-AM is actually doing very well.
Yes.
No, that's right. We've still got 40 seconds, so I should ask.
TEBE advanced melanoma.
Our enrollment is moving according to time. We expect the first half of 2026 to finish our enrollment, data shortly after that. That is an sBLA for KIMMTRAK. Obviously, high on med needs setting, first phase III trial that is looking at overall survival as an endpoint in this patient population. We have high expectations. We have the ATOM study in the adjuvant uveal melanoma setting. It is the only phase III registration trial in the adjuvant setting. The PRISM -MEL phase III study. Three phase III studies in melanoma that are going to be reading out over the next few years.
Perfect. Thank you so much.
Thank you, Peter.
Thank you for having us.
Have a.