Immunocore Holdings plc (IMCR) Earnings Call Transcript & Summary

Okay. Good afternoon, everybody. Thanks for joining us at the Bank of America Healthcare Conference. I am Tazeen Ahmad. I am one of the SMID biotech analysts here. Our next presenting company is Immunocore. Presenting for Immunocore is Brian Di Donato. Brian, good afternoon. Thanks for making the trip out West.

Thanks for having us, Tazeen. This is our first Bank of America conference at Immunocore.

Yes, we hopefully don't disappoint.

Very well attended.

And for anybody who doesn't know, Brian is, of course, CFO of the company. So maybe, Brian, before we get into the specifics of Q&A, it might help to give an overview of Immunocore, like a 2-minute elevator pitch, and then we can go into more detail.

Yes, happy to. So we're a commercial-stage biotech company that has the first TCR therapeutic for solid tumors. So we have the first commercial product called KIMMTRAK. I'll talk a little bit about that. We had earnings this morning and we talked about that. But what we do is we reengineer T cell receptors into bispecifics. And we can use that bispecific to engage your -- the body's own immune system, CD4, CD8 T cells, to kill cancer cells or to kill infectious disease targets like HIV is one objective of ours, or we could use that engagement, that high affinity engagement that is very specific for a target, to turn down the immune response in autoimmune. So we're also -- the team -- our engineering team is working on that. We have over 100 PhD protein engineers in Oxford, England. That's where the company was founded. So they've been doing this for 15 years, creating soluble, off-the-shelf bispecifics to engage targets.

Perfect. So it's a very unique profile that your company has created for itself. And I think what we find particularly interesting also is that you're both commercial and pipeline at the same time. So you're still in the early innings of your KIMMTRAK launch. Maybe talk to us about how that's going in uveal melanoma, where you've been able to have a surprise upside, and what you think the additional opportunity could be there.

Sure. So our bispecifics need to be designed for a specific HLA type. So initially, all of our clinical candidates right now are HLA-A*02. And for uveal, that's around 50% of the Western population is HLA-A*02. It's different by disease type. And so we launched a little over a year ago in the U.S., about a year ago in Europe. We reported earnings this morning. We had $52 million net sales for the quarter. We had $51 million of net sales in Q4. We continue to see good growth in the United States. We have about 5% growth quarter-over-quarter of vial sales in the United States, about a 20% growth in Europe. Right now in Europe, we're reimbursed in -- or paid in France and Germany. We haven't reached final reimbursement agreement. We'll talk about that. But it's really 3 countries: U.S., France and Germany to generate that -- those sales. Growth opportunities exist in the United States. We're about 50% penetrated in our math in the United States, where about 50% of those patients are first line. So more -- about 55% are first line. So more to go on getting first-line patients. We know for this mechanism that treating early is better. In our Phase III clinical trial, if you had tumors that were less than 3 centimeters in the liver, the hazard ratio is 0.36 versus an impressive 0.51 hazard ratio for the Phase III trial overall, mostly versus PD-1 checkpoint inhibitors. So we have some growth levers, we think, for -- or growth opportunities for further sales and patient engagement. In addition, in Europe, we're going to add Italy by July. So we should have patients reimbursed in Italy in July and then 4 other European countries later this year.

Okay. So maybe just drill a little bit further into some of the things that you said. So you've already gotten 50% penetration, you said, and your launch is pretty new. So was that what you were expecting? And if it wasn't, what was something that you didn't anticipate that allowed you to have a steep uptake?

Yes. The good part is that this is the only approved therapy for HLA-A*02-positive metastatic uveal melanoma. It's a pernicious disease. The survival has been historically 10 to 12 months. So we had about 25 clinical trial sites in the Phase III in the U.S. Those physicians were really excited about converting those patients. And then we've grown from there in the United States. So our focus right now is getting out to the community. Historically, even though not approved, ipi/nivo has been the go-to therapy for medical oncologists in this space, even though that has not had a -- has had a modest survival benefit. So it's important to get that word out in the community. So we're now we're also 50% in the community in the United States. So that's exciting in 12 months in that we've made those strides. More to go though.

And how do you think about durability for patients?

Yes, great question. So in the Phase III, our duration of therapy was 9 months globally. And I can say that we're about 9 months already in the first year of launch. We did have a pretty extensive early access program. So we gave the drug for free. Once we had the Phase III data globally, over 200 patients globally, we're on the early access program before we launched. And what we're seeing is that 9 months is definitely the real world matching the Phase III. We had some data at AACR in a month ago that showed in the Phase II, which was late-line patients that the duration of therapy is now 10 months. And we've had patients on for 4 years. So more to come on duration of therapy in the future.

Okay. And so what would be your strategy now to move into the earlier lines of the 50% or so that remains?

Yes. So first line, we are first-line approved and [ many-line ] approved for KIMMTRAK. I think when we think about where we want to go with this, what we also see now with PRAME is that in uveal as well, we've had a 50% RECIST response in our initial patient population for uveal. So we know PRAME as a RECIST response drug given the high prevalence and the high copies per cell that is presented. So PRAME definitely has an opportunity to move even earlier potentially to adjuvant as well. And KIMMTRAK has the opportunity to move to adjuvant as well is where we ultimately want to be.

Okay. Now you are looking at additional indications, of course. Can we talk about expansion into cutaneous?

Yes, absolutely. So what we know in a first-line trial is that KIMMTRAK works both in uveal and cutaneous. It targets a protein called gp100 in melanocytes. So makes sense. And what we know about the cutaneous opportunity is in the first Phase I, the 1-year survival was 75% to 77%, depending if you had a PD-1 or no PD-1 on board with you. And that compares favorably with about a 55% 1-year survival for other late-line melanoma therapies. So we believe that there's a role for KIMMTRAK in late-line melanoma. So we've designed a trial that's a Phase II into Phase III trial randomized. So one arm will be KIMMTRAK alone, one arm will be KIMMTRAK and KEYTRUDA, and then the other arm is effectively investigator choice, which we'll follow for survival benefit. The Phase II endpoints are 1-year survival, like we had in the Phase I. And also circulating tumor DNA reduction, which we have found is highly correlated with survival benefit. So you take a circulating tumor DNA sample at baseline and then compare that with 9 weeks into treatment. And what we found is that if you are reducing your circulating tumor DNA in the Phase III for uveal, 88% of the patients who reduced their circulating tumor DNA, 37% cleared it. And that is directly correlated with survival benefit. Why is that important? Because we know in cutaneous, we see the same correlation. So we think for the Phase II portion, to know which arms to take in the Phase III, that will be informative. And so what the plan is, is to drop an arm, so drop either the KIMMTRAK plus KEYTRUDA arm and compare that to investigator choice, or drop the KIMMTRAK alone arm. But these patients have already seen a checkpoint inhibitor. So we'll see.

Okay. So when does the next data readout coming out?

The Phase II, we should know by the end of next year, end of '24. We should have a clear read on some top line results and what the path forward is for the Phase III.

Okay. Now are you in a position to really talk about the expected market opportunity in cutaneous?

Yes.

And then how much bigger it could be than uveal?

Yes. So the uveal market opportunity in HLA-A*02 positive, which I said was about 50% of the population in the West, is around 1,000 patients a year is our estimation. And the late-line cutaneous population could be 2 to 4x that. So 2,000 to 4,000 patients a year is the opportunity.

And would that be distributed equally over the U.S. and Europe?

Probably, it's pretty evenly spread.

Okay. We didn't talk about this. You just talked -- you touched upon it. But as far as uveal melanoma in Europe goes, how do you think about the trajectory there versus what you've seen here?

Yes. The penetration rates in Europe are higher for France and Germany. That's our 2 launched countries right now, probably 75% penetrated in France and Germany.

And is that because patients are really concentrated in certain sites?

It's a better connected medical system in France and Germany. Maybe the smaller countries, maybe the physicians are connected better, but it seems to -- we're now 80% first-line patients in France, 70% first-line patients in Germany. So really good inroads in both those countries. Duration of therapy continues to extend in both. So we did see 20% growth in Q1 in both those countries.

And so as you look at cutaneous, would you -- how would you divide up that opportunity as well? Would it be leaning more towards Europe as well or more equal?

No, I think it'd be more equal. In patient numbers, it's more equal. Reimbursements, we'll see what the reimbursement landscape is at that time.

Okay. And then going back again to uveal melanoma, I think I forgot to ask you whether the nonmetastatic opportunity would be attractive because doctors have talked about that.

Yes. So what's interesting about uveal is there's a couple of chromosome mutations that predict -- highly predict metastasis. So if you have one or both of those mutations, you're likely to metastasize. So the adjuvant therapy is really interesting to us. And I think KIMMTRAK and PRAME both lend themselves well in that they're extremely low dose, they're microgram dosing, they're highly specific for the target, lend themselves well to the adjuvant opportunity. So yes, we're thinking about how to best...

Would you need a study for that? Or could doctors just kind of use it off-label?

Yes. You would need a study. So we're doing a study in an investigator-sponsored study in the U.K. that tracks circulating tumor DNA, so before metastasis. So once you see an increase in circulating tumor DNA, then you would get KIMMTRAK. And that's a pretty novel approach that the investigator was interested in and we were interested in. So we're funding that. And then we're looking at other ways to fund adjuvant studies.

So how much would that increase your opportunity in uveal if you were to expand into nonmetastatic?

Yes, great question. I mean most of the patients, unfortunately, are going to metastasize ultimately. So I'm not sure it's that great, but it's better for the patients to treat them earlier.

Does it slow it down, like progressing into...

Yes, we would think so. I mean we think that it would be a great inhibitor of micrometastasis.

Yes. Right. So that would seem to be a value add?

Absolutely.

Okay. So maybe let's move on to PRAME. Can you give us a more detailed overview of that program? What it is? And what indications you feel it could be potentially meaningful to pursue?

Yes. So PRAME is highly prevalent. It's a cancer testis antigen. It's an intracellular protein that is a negative prognostic marker for many tumor types. So the tumor cells hijack the protein PRAME to live longer and to expand. So PRAME is only presented in cancer cells. So it makes it an ideal target. And we think we found the right peptide to target on the cell surface. And in our data that we shared at ESMO, it would coincide with that, that in uveal patients, that we had a 50% response rate. In cutaneous patients, we had a 33% response rate and a couple of other patients that were pretty near partial responses. And then in ovarian, a 50% response rate. And in 3 of the 4 lung patients had circulating tumor DNA detectable, and those all reduced circulating tumor DNA by 50%, even though the patients were only on PRAME for a couple of months because these are really late-line patients. So it gives us reason to believe that this high prevalent protein that is present in those tumors that I just mentioned is really an ideal target. So not only are we -- do we have an A*02 allele that we mentioned is 40% to 50% of the Western population, we also have an A24 allele for PRAME. That is going to be in the clinic next year. And that is -- more than 60% of the Japanese population is A24, and another 15% of the West is A24. So when you put -- in Japan, if you put A*02 and A24 together, it's about 80% of the Japanese population and about 60% of the Western population with A24. Thirdly, we think that we want to explore the half-life extended version. Right now, our molecules are dosed weekly, have a biological half-life of several days where they create a cytokine release and killing, and then you redose. And that redosing, we think, is really important for durability over time in bringing fresh T cells, CD4 and CD8 T cells in the tumor microenvironment. So we do want to explore what a half-life extended version may bring. So we have one of those in the clinic next year as well.

Okay. So maybe let's back up a little bit on data for PRAME. So at last year's ESMO, you presented a number of patients' worth of data. I think initially, it might have been misinterpreted, but I think it's been corrected. But just to remind everybody, can you give us a summary of what you had shown?

Yes. Yes. No, I think it was really informative for us to see the responses that we did, given the high prevalence for PRAME. And when you do have the PRAME protein, you generally have a high H-score. So our median H-scores were in the 180s for PRAME, whereas for a molecule -- or for a protein like MAGE, which we had a MAGE program, the median H-score was below 50. So given that prevalence where it's 90% prevalent in melanomas, it's 80% prevalent in ovarian, 70% prevalent in squamous lung, somewhere in the 60% prevalent in adeno lung. That's what made it the ideal target. I think on the data set that we had at ESMO, we did have those responses that I mentioned. I think there's some speculation that we'd have lung data, lung responses, and that was really stock speculation, I think. We didn't infer that we were going to have that. It was still early. It's Phase I data. So after that initial week or 2, the stock seeming to rebound really well based on people going through the data.

Yes. So what did you learn specifically about non-small cell lung? I think it seems that the reason people were particularly excited is because of the large indication.

And it's prevalent, yes.

Yes. So what did you learn from that initial cut of data that you saw and you're obviously now taking action based on what you saw there. If you could talk about that study.

Yes. What we learned was that these patients, as I said, were only on therapy for a mean of 2 months, which isn't long, that even with that, we saw the circulating tumor DNA reductions of 50%. There's a study by the Friends of Cancer Research. It's a meta-analysis of 6 different studies that show that if you have a 50% reduction of circulating tumor DNA, that portends well for survival benefit. So that gives us reason to believe. We do need to get earlier line patients with -- that are immune fit in lung. So we know that. And that's what we're focused on now. The team is focusing on enrolling and opening trial sites in lung-specific academic centers and working with physicians to enroll healthier lung patients.