Good afternoon, everyone. I'm Rajan Sharma. I'm one of the healthcare analysts here at Goldman Sachs. I'm pleased that we've got Immunocore to join us for a fireside this afternoon. We've got Bahija Jallal, who's the CEO, and Brian DiDonato, CFO. Maybe I'll pass it over to you guys. Could you just maybe introduce yourselves, give us a bit of background on yourselves, and maybe make some high-level comments on the company and kind of the trajectory that you've been on over the last 12 months or so?
Sure. Thank you for having us. I'm Bahija Jallal, I'm the CEO of Immunocore. I joined almost 4.5 years ago. Was president of MedImmune/AstraZeneca for almost 13 years, and before that, was in the Bay Area, Sugen and Chiron. Yeah, I joined the company for really the outstanding science, and they believe in the platform. Since then, we have, you know, an exciting platform that not only can work in three therapeutic areas, but validated now in the clinic, and be happy to talk more about that.
Brian DiDonato, Chief Financial Officer and Head of Strategy. I joined Bahija about a little over three years ago. Also because of this elegant science and the opportunity to take a private company to the public markets, given the commercial opportunity we had ahead of us. Prior to this, I was CFO of another public company called Achillion, which is also in the immunology space, that was purchased by Alexion.
Perfect. kind of, you spoke to Bahija, I guess, on kind of the multiple technologies, et cetera, and the indications that you have. From a high level, could you just remind us as to where you are, the kind of the key parts of the R&D story here?
Yeah, definitely. Our platform, which is really one of the characteristics and differentiation with the platform, is that it has a soluble TCR that's on one hand, it basically binds to the tumor cells, and on the other side is. This TCR, T-cell receptor, we made it soluble at high affinity and specificity. On the other side, we have the anti-CD3 that will bind to any CD3- positive T-cells. What it does is redirect any T-cell to bring them then closer to the tumor and kill the tumor. Why is that differentiated?
You know, one is, it's because it binds to a peptide presented by HLA complex, it will have access to almost 90% of the proteome, because every intracellular as well as extracellular protein will be degraded and presented. We have access to more targets. The second differentiation, it is off the shelf, if we compare, for instance, to cell therapy, it's off the shelf really an easy and repeatable and cheap, actually cheaper, you know, manufacturing. That's some of the advantage, and also we are bringing fresh T-cells every week, if you will, to the tumor. That's really the aspect.
The other aspect is that in the effector arm that we have, we can use the CD3 or anti-CD3 or anything that could upregulate the immune system. That works for tumors as well as infectious disease, for instance, so to kill the tumor cell or the infected cells, and we actually have programs in both. On the other side, we can put as an effector function, you know, something to down modulate the immune system, and we have a proof principle now in preclinical showing that we can use an agonist for PD-1 agonist, for instance, to go very much organ-specific down modulation of the immune system, which then could tackle several of the autoimmune diseases. Those are the aspects. That's a very modular platform.
Of course, the most important aspect of that is that this was the first soluble TCR bispecific to be validated in the clinic. That with our first product, which is, you know, against the tebentafusp, which is the gp100. Now KIMMTRAK is on the market, has been showed an overall survival, which has a ratio of 0.56, which is really amazing. It validated the platform. This is the first TCR bispecific to show overall survival in solid tumors, which is important. That's the first TCR to be approved at all. Also, which is really important, is the first medicine to be approved in uveal melanoma in four decades.
That basically gives us now the confidence to go after the next generation and the next generation. We have programs with PRAME and PIWIL1 coming, and I'm also trying that in infectious disease. For us, it validated in human, in the clinic, the whole, the whole platform, which then opens up really a lot of possibilities.
Okay. Obviously, you touched upon it, but obviously last year was a very important year with the approval and the launch of KIMMTRAK. Could you maybe just kind of provide your thoughts there, how successful the launch has been relative to your expectations, and kind of initial feedback that you've been receiving?
Yeah, definitely. I think I'll let Brian talk more about the KIMMTRAK. You know, we decided to commercialize the drug ourselves because we are, as we continue to learn about the platform, we are now bringing really the learning from the market to even inform even better, how we do the clinical trials and how we do research and all that. That was very important for us. We have been extremely happy to see that, you know, what we have seen in the clinical trials, which are very controlled and everything, are true in the real world and helping a lot more patients across the world, and we're very happy with the results. Brian can talk a little bit about our performance there.
Yeah. KIMMTRAK is approved for metastatic uveal melanoma if you're HLA-A*02:01 positive. As Bahija said, all of our TCRs target initially HLA-A*02:01, which for uveal melanoma is around 50% of the population. The market opportunity is around 1,000 patients a year, we estimate, between the U.S. and Europe. Rajan, last year, we launched in the U.S., France, and Germany. In those three countries, our net sales were $140 million. We're still experiencing growth, which is great. We're about 50% penetrated, maybe a little bit more in the United States, more to go in the United States. The outreach is happening with our sales team.
Duration of therapy, not only in the U.S. but globally, is around nine months, is what, as Bahija said, what we saw in the phase III. Hopefully, we'll continue to extend as patients get treated earlier and earlier in their disease course. France and Germany, about 75% penetrated. Pleased with what the team has done there. We still are in the reimbursement phase with France and Germany, until we have final reimbursement, we take an accounting assumption for France and Germany. We'll true those up once we have final agreement. We announced in first quarter earnings about a month ago that we're also looking to launch in Italy by July.
Excited about that, and looking to expand the European footprint, not only in Italy, but probably five other European countries later this year.
Okay. I think it's fair to say that the kind of launch of the product and the quarterly numbers that you're booking kind of surprised the market versus what consensus was. It could be because we weren't modeling it correctly, but how did that compare to your initial internal expectations?
Yeah, it was pretty consistent. I think one of the successes with the commercial launch for us was having an early access program. We gave the drug away. Once we saw the phase III data, we went to great lengths to make this drug available for free to patients, and it's been available to over almost 1,000 patients for free since the data, phase III data. Then we were able to transition those patients once we do get reimbursement agreement by country, to commercial payers, to commercial paying customers. It's a win-win.
Okay. I guess when you think about the trajectory from here, one of the questions that I always get from investors is kind of: Well, what's the ultimate opportunity here? You've talked about kind of patient numbers, how do you see the growth from here? Is that duration? and driving that penetration?
Yeah. I think it depends if you ask patient numbers or sales.
Mm-hmm.
For sales, the U.S. is probably 60% to 65% of sales right now. As we add European countries, it may become a little bit less, but we still have more to grow in the United States. We have patient numbers to grow in the United States, which will convert hopefully to sales. Europe, as well, Canada, Australia, will be a sequence over the next 18 months or so. In addition, again, as I mentioned, Bahija mentioned a hazard ratio of around 0.5 for the phase III. In a cohort analysis, if patients had tumors less than 3 centimeters, the hazard ratio is 0.36. Getting patients treated earlier is better for the patient journey. We don't know what that duration of therapy will be.
As Bahija said, we're gonna update the phase III data later this year. We'll present that data with more longevity.
Okay. how should we be thinking about the European opportunity, given obviously, KIMMTRAK, kind of a rare, in a, in a rare indication, high priced, and how are you thinking about that?
Yeah, two components of the European reimbursement process. One is the health authorities, and we're excited that both France and Germany had KIMMTRAK among the highest rated for oncology therapeutics given its survival benefit with the gold standard. It's the only approved therapy for metastatic uveal melanoma for HLA-A*02:01 positive. That's great. Then you go to the reimbursement process, and that just takes time. You work through that again, with the medical benefit that it provides and the survival benefit. We're confident that the payers will see the value for patients of KIMMTRAK, that's a process over the next 18 months or so.
Okay. You're obviously investigating the drug in other forms of melanoma, cutaneous melanoma, for example. Could you provide us the rationale there and bring us up to speed as to where you are?
Yeah. When we think about KIMMTRAK, the target is gp100, it's exclusively expressed in melanocytes, and in this case, in uveal melanoma and in cutaneous melanoma. We have done previous trials, seeing, you know, in cutaneous melanoma, and we know it works there. One year survival was around 76%, which I think when you compare to whatever is out there, it was 55%. We believe it will work. Also it really emphasizes that this technology can work in checkpoint sensitive and non-sensitive tumors. That's one of the pluses. We are actually looking at...
doing a phase 2/3 trial, looking at, in the previous trial that we've done was, also we, added to PD-1, and the combination went well. We are looking at, we agreed with the FDA on the design of the phase 2/3 trial, where we look at, either, a KIMMTRAK by itself, KIMMTRAK plus PD-1, and then, direct to survival. This is pretty a novel design. In the phase II portion, we will be looking at, you know, if we have ctDNA, as which we looked at the reduction, and then, trend of OS will drop once or we will power the trial differently for phase III. That will guide us basically to go into phase III.
That's where we're looking at KIMMTRAK again, which we believe will have also an impact in cutaneous melanoma.
Okay. Brian, maybe just the incremental opportunity that brings to you, and then also within that, if you could kind of help us understand pricing and whether the high price in uveal then translates to larger indications?
Our estimates are that in late line cutaneous, the opportunity is several thousand patients, so maybe 2,000 patients to 4,000 patients a year versus 1,000 that we have for metastatic uveal for KIMMTRAK. On pricing, it's too early to tell. We'll have to see the data and see the benefit to patients and see where the competitive landscape is at that time.
Okay. Talking about the competitive landscape, maybe just going back to uveal here, we've seen some data recently from kind of other therapeutics that are in development, particularly if you think about some that may not necessarily have the HLA cut-off. How do you think about positioning of KIMMTRAK against that?
Well, you know, so far, you know, KIMMTRAK, we believe, is the standards of care in HLA-A*02:01 positive. Anything in the HLA-A*02:01 positive patients have to show better OS. That's the ultimate end point. I think on HLA-A*02:01 negative, you know, there is an unmet need. Obviously, there is nothing for these patients, and we're happy that this is gonna be tested in HLA-A*02:01 negative. That's basically what how we look at it.
Okay. Okay. Then maybe kind of moving on to what's next after KIMMTRAK and PRAME is an area that we've obviously been interested in, and the industry is becoming more interested in that. Bahija, maybe could you just outline why there's the excitement there from kind of a high level, and then we can kind of think about how you fit?
Yeah. Once we validated the, you know, KIMMTRAK and the platform as a whole, the next step we had already accelerated PRAME from the beginning because it had several of the characteristics. If you think about, you know, what's gonna be really different from a KIMMTRAK, you know, this just basically the construct is the same, except the peptide and the HLA that you bind to it. PRAME by itself is a really an interesting target because it's highly expressed in expressing multiple tumor types, not only it is in melanoma, but outside of melanoma as well.
The other characteristics is, whenever PRAME is expressed, it's highly expressed and homogeneously expressed, which is important, you know, in multiple tumor cells and at a higher intensity. The third thing is that it is also a negative prognostic marker. That means that the tumors tend to wanna keep the expression of PRAME. For all these things, we think it's exciting. Then we did the phase I that we presented last year at ESMO. In phase I, usually, especially with our platform, because it's all humanized, we don't do any animal studies. We start at a very, very low dose, at MABEL dose, what we say the MABEL dose.
It was, and in phase I, usually, you're really looking at more safety and, you know, the dose. We were happily, you know, we saw data that was really exciting. We saw 50% ORR in cutaneous melanoma, 36 in uveal melanoma. We saw 50% in ovarian. Again, the numbers are phase I numbers, but the totality of the data was in, pretty, it was over 30 patients or so. That was really the, what you wanna see in a, in a, in a drug. One is we saw the pharmacodynamics going in the right direction, and we see activity that was at pretty low level, at 20 micrograms or something like that.
That is, for me, you know, being in this field for so many years, to see this kind of data in phase I was absolutely exciting. Subsequently, that was confirmed in a different platform, in a cell therapy platform, so that the PRAME is a really validated target as far as I'm concerned. You know, from there, we are now obviously capitalizing on this data to then continue the development of PRAME.
Okay. Could you maybe just discuss kind of the strategy in terms of trial design and, you know, enriching for PRAME? I think in your phase I, you didn't enrich, whereas some of the other players in the field have. Be interested to get you the rationale around that.
Yeah. If you think about, that's one of the differentiator also with our platform. If you look at, you know, we increase the affinity of the binding to the target with 1 million times. We are in the picomolar level, so we know whether we can kill cells down to five to 10 copies per cell. Our, you know, our platform is very potent. We didn't enrich because we have seen with tebentafusp and with KIMMTRAK that, while to see a RECIST response, you had to go with really high, what we call H-score. The overall survival, it didn't matter if you were a low expresser or high expresser, that comes, in my opinion, to that exquisite potency that we have.
In the case of PRAME, you know, like I said, the expression is pretty high to start with. In multiple tumors, we didn't do. We looked at the expression retroactively, not prospectively. That was, I think, you know, enough. It depends, again, what you're gonna be looking for. For the resist, yes, it matters, but in this case, it's highly expressed anyway. We continue now, you know, tumor by tumor, you know, we'll consider what the expression and so on.
Okay. Just if you, on that comment, kind of tumor by tumor, what do you think are kind of the most promising and most interesting, and I guess kind of beyond melanoma, because, you know, the push factor may be that that's kind of one of the less difficult tumors to kind of treat from that perspective? How do you think about kind of potential beyond melanoma?
You know, just where we started, you know, for me, frankly, in any, anywhere where PRAME is expressed, I would like to go and explore it because it's such a powerful platform. We started where the expression is high, basically, and where we saw signals as we would do in any other drug development. We started in uveal melanoma, cutaneous melanoma, ovarian endometrial, because it's really high expression there, very high, and also lung, to explore the lung. That's where we now did the expansion, which we call the expansions, to confirm what we've seen in phase I, to confirm the activity. In parallel, we're looking at doing the combination. We opened the combination with PD-1, combination with chemotherapy, and then with tebentafusp.
Just to have a kind of a safety running in that when, depending on the line and the indication, we can move into a combination with standards of care.
Maybe could you just kind of discuss the wider PRAME strategy, because you obviously have multiple shots on goal there, and you kind of made the decision earlier this year where that was the focus over MAGE-A4, for example. Could you just kind of run through the strategy?
Yeah, it was, it was really an easy decision, and that's where, you know, the prioritization in the, in the pipe- You know, we are in a good situation where we can prioritize in our pipeline, which is great. I think, you prioritize based on data. When we started the MAGE-A4, as well as we started the PRAME after, you know, looking at the data with MAGE-A4 and the expression, we know there is activities, an active molecule. The, wherever PRAME is expressed, MAGE-A4 is expressed as well, or vice versa. Wherever you see expression of MAGE-A4, we see expression of. There is a lot of overlap between that and PRAME, and PRAME tends to, the prevalence tends to be even higher.
I think it made a lot of sense for us, having two molecules, like this, to go ahead and focus, solely on PRAME, and that's exactly what we did.
Okay. Then could you just remind us kind of next data points for the PRAME assets?
Yeah. By half of, by the first half of next year, I think we said we'll do that. This year is really about executing the trials. It's several trials going on right now, the phase 2/3 that we talked about, the expansions and all that. We hope to have data by, you know, first half of next year.
Okay. You also have the, kind of the product that's targeting HLA-A24. Could you just talk about rationale there and what that may mean in terms of incremental patients that you can target?
Yeah, absolutely. That's really exciting, as I think we said it is HLA-A2 restricted. When we talk about KIMMTRAK, for instance, we know not only where the HLA-A2 is a Western, is in the West, but when we look at the disease itself, it's mostly a Western disease, where HLA-A2 are. It's very different with the when we look at other tumor types now or PRAME, and that's why we made the decision to go after A24, because, for instance, in Asia, like just in Japan, the expression of A24 is around, I think, 60%, which is pretty high. If you add, they have also some A2, so if you take the two together, it's around 70%.
I think it would make it worth it to go and make the molecule against the HLA-A24, that we can expand that into Asia. That one, hopefully will get into IND by first half of next year.
Okay. Just as you know, we talked about kind of PRAME being increasingly in focus area, we've seen some data in cell therapy. We have your data that you... How do you look at kind of the competitive landscape? Do you think it's beneficial that there's multiple players doing the work here?
Yeah, so I'll just say, you know, look at HER2, right? You know, I do believe that the good thing, the very good thing, is that it shows always, you know, that PRAME is a very attractive target, right? I think the populations that are, you know, are amenable for cell therapies are maybe more restricted. I think we're definitely, it's a great target to go after.
Okay. Maybe kind of just switching focus slightly to the infectious diseases part of the business. I guess we saw some early data from HIV this year. Could you maybe just kind of contextualize that for us?
Yeah, it's really, at least for me, the concept is exciting, and I think we are privileged and happy to test that concept. If you think about the HIV, thank goodness, it's becoming now, a very, you know, chronic disease. You know, people don't die from their HIV. Having said that, you know, this is why we do what we do, is you're not satisfied just with that, people have to take their medicine every day or all the time, all their life. If they stop, what happens is that you have the viral load that basically, you have a rebound.
That's because there is a reservoir that's very small reservoir, the virus hiding in the CD4 cells, and that's the actual technologies right now have not been able to attack this reservoir. With what I said about the technology being so potent, you know, that we can go kill down to five to 10 copies per cell, it behooves us really to go and test that. If we can be with that potency, go after that reservoir, we can help the people living with HIV not to have to take this. You know, there's a lot of issues with taking medicine all the time.
You know, there's a compliance issue, you know, if you don't, if you skip or something like that, then every time you have an increase of the viral load, you're more subject to mutated virus and things like that. And also, you know, drug-drug interactions if you are taking other medicines. It's not easy to just say, "Okay, well, they can just take it all their life." That's really what we're trying to do. The phase I that we did, which is the single ascending dose, first of all, it was just great for us on HBV to go, HBV and HIV, to go outside of oncology. The trial accrued very quickly, which was... It's always a good sign in drug development, so this was good.
But most importantly, what was really exciting is we saw in this single ascending dose, we saw a target engagement, what we call target engagement. We saw that through an increase, dose-dependent increase of IL-6, which for us means that we engaged the target. That was very, very exciting. Now we are doing the multiple ascending dose. That's recruiting right now, we are actively doing the trial is open and is accruing. In that one, what's really interesting is that we'll have the patients are dosed with their antiviral, so the viral, the antiviral and the ImmTAV, our molecule, for 12 weeks. They take the medicine for 12 weeks, we stop everything, and then we look for the viral rebound.
Meaning that with this trial, we will have a proof of concept one way or the other. That's exciting, and that's ongoing, and we hope we can make a difference for these people living with HIV.
Okay. I think in the phase I, there was kind of very low rates of CRS, right? Is that?
We don't see CRS actually in these patients.
Okay.
which is great.
I guess one thing sometimes that we hear on that as a kind of a, maybe a bit of a pushback, is that does that mean there's any risk that there's not kind of sufficient engagement of the immune system because you're not seeing the CRS?
What, the, it's maybe true if in oncology and why we see a CRS in oncology, because you have only the target load is a lot more and so on. Here, you know, you're really exquisitely to the virus and it's the target is a lot less. You don't have to deal with the whole microenvironment and how much of the drug that you have to bring there. We are talking about 15 micrograms, but I would have worried if we don't see any increase. It's actually, it's in a very interesting, you know, dynamic because of that lack of tumor microenvironment and everything. Even how fast the...
You know, you get the peak with the oncology very quickly of cytokines. That's, we believe, what creates the whole CRS, right? You have that. In the HIV is a lot more, you know, goes a little bit slower, not as fast up. Goes slower. We believe that's what avoids the CRS. I think it's a good sign, frankly, that we see that increase in IL-6. I would have worried if we don't see anything, you know?
I guess, Brian, in terms of kind of strategy on the, on the infectious disease side, is that something that is, you know, better done by Immunocore, or could that be partnered out and there may be a better owner of that?
I wouldn't say the infectious disease side generally. I think the way we think about partnerships is per molecule or per disease type. For HIV, if we see a signal, and see a path forward, yes, we can start having partnership conversations, because those could be large trials, and having external experience in HIV would be really helpful in a large trial. We would look for partnerships there. I think we take each molecule separately on when the optimal time to partner them is.
Okay, conscious of the time, but just in terms of cash, could you just remind us where you are in terms of liquidity?
Our cash has gone up for each of the last three quarters now, I believe. We're in great shape and can fund all the trials we need to fund for the foreseeable future. We, we say publicly that we're funded into 2026, so call it three years of cash runway. We have over $400 million of cash right now.
Okay. Could there be a scenario where you may not necessarily need to kind of go back to the markets to raise additional capital?
Are you asking me what peak sales are for KIMMTRAK? It's too early to tell.
Okay.
It's too early to tell what peak sales will be for KIMMTRAK, and it's too early to tell how many pivotal trials we'll need to run for PRAME.
I won't ask you what peak sales will be for KIMMTRAK, but when do you think you may have a better idea on what peak sales might be?
Yeah. We have to finish the reimbursement agreement with France and Germany.
Mm-hmm.
That'll be sometime over the next six to nine months. We'll announce that when that is complete. The duration of therapy, we'll share the phase III update on the duration of therapy later this year. Maybe by early first half of next year, we should have a better idea of being able to guide for an annual sales number.
Okay, perfect. Maybe just in the last kind of 20 seconds or so, could you just kind of remind us of key catalysts as we get into next year and what you guys are particularly excited about?
Well, it's definitely, you know, the data, as we said, by, you know, first half of the year will bring data for PRAME, and then we'll bring also the data for HIV, so the multiple ascending dose. We also have the new, hopefully the newcomers, the PIWIL1. That's the new target, that we set the IND by end of this year. Hopefully starting then, to enroll next year. We'd have the IND next year for PRAME A24 and PRAME half-life extension. A lot happening.
All right, brilliant. Thank you so much.
Great. Thank you.
Thanks Rajan.