Okay. Good afternoon, everybody. Thanks for joining us at the Bank of America Health Care 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 hope we don't disappoint. Very well attended. It's great. For anybody who doesn't know, Brian is, of course, CFO of the company. Maybe Brian, before we get into the specifics of Q&A, it might help to give a overview of Immunocore, like a two-minute elevator pitch... Yes. Then we can go into more detail. Yeah, happy to. We're a commercial stage... -biotech company that has the first, TCR therapeutic for solid tumors. We have the first commercial product called KIMMTRAK. I'll talk a little bit about that. We had earnings this morning. I can talk about that. What we do is we re-engineer T-cell receptors into bispecifics, and we can use that bispecific to engage 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. We could use that engagement, that high affinity engagement that is very specific for a target to turn down the immune response in autoimmune. We're also. Our engineering team is working on that. We have over 100 PhD protein engineers in Oxford, England. That's where the company was founded. They've been doing this for 15 years, creating soluble off-the-shelf bispecifics to engage targets. Perfect. 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. 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, you know, what you think the additional opportunity could be there. Sure. Our bispecifics need to be designed for a specific HLA type. Initially, all of our clinical candidates right now are HLA-A*02:01, and for uveal, that's around 50%. of the Western population is HLA-A*02:01. It's different by disease type. 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 had 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. It's really three countries, the U.S., France, and Germany, to generate 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, 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. We have some growth levers we think for, or growth opportunities for further sales and patient engagement. In addition, in Europe, we're gonna add Italy by July. We should have patients reimbursed in Italy in July and then in 4 other European countries later this year. Okay. I'd maybe just drill a little bit further into some of the things that you said. You've already gotten 50% penetration, you said, and your launch is pretty new. Yeah. Was that what you were expecting? If it wasn't, what was something that you didn't anticipate that allowed you to have a steep uptake? Yeah. The good part is that this is the only approved therapy for HLA-A*02:01 positive metastatic uveal melanoma. It's a pernicious disease. The survival has been historically 10-12 months. We had about 25 clinical trial sites in the phase III in the U.S. Those physicians were really excited about converting those patients. We've grown from there in the United States. Our focus right now is getting out to the community. Historically, even though not approved, ipi/nivo has been the- The go-to therapy for medical oncologists in this space, even though, that has had a modest survival benefit. It's important to get that word out into the community. We're also 50% in the community in the United States. That's exciting. Yeah. 12 months in that we've made those strides. More to go, though. How do you think about durability per patient? Yeah, great question. In the phase III, our duration of therapy was nine months globally, and I can say that we're about nine 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 were on the early access program before we launched. 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. We've had patients on for four years. Yeah. more to come. Yeah duration of therapy in the future. Okay. What would be your strategy now to move into the earlier lines, the 50% or so that, that remains? Yeah. first line, we are first line approved and- ...any line approved- ...for KIMMTRAK. I think when we think about where we wanna 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. We know PRAME is a RECIST response drug given the high- ...prevalence and the high copies per cell, that is presented. PRAME definitely has an opportunity to move even earlier, potentially to adjuvant. ...as well. KIMMTRAK has the opportunity to move to adjuvant as well. Is where we ultimately wanna be. Okay. you are looking at additional indications, of course. Can we talk about expansion into cutaneous? Yeah, absolutely. 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. What we know about the cutaneous opportunity is in the first phase I, the one-year survival was 75%-77%, depending if you had a PD-1 or no PD-1 on board with you. That compares favorably with about a 55% one-year survival for other late line- melanoma therapies. 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. 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. You take a circulating tumor DNA sample at baseline and then compare that with 9 weeks into treatment. What we found is that, if you are reducing your circulating tumor DNA in the phase III for uveal, 88% of the patients re-reduced their circulating tumor DNA, 37% cleared it. That is directly correlated with survival benefit. Why is that important? We know in cutaneous we see the same correlation. We think for the phase II portion to know which arms to take into phase III, that'll be informative. What the plan is to drop an arm. Drop either the KIMMTRAK plus KEYTRUDA arm and compare that to investigator choice or drop the KIMMTRAK alone arm. I see. These patients have all already seen a checkpoint inhibitor. Right. We'll see. Okay. when is, that, the next data readout coming then? The phase II, we should know by the end of next year, end of 2024. We should have a clearer read on some top-line results and what the path forward is for the phase III. Now, are you in a position to really talk about the expected market opportunity in cutaneous? Yeah. How much bigger it could be than uveal? Yeah. the uveal market opportunity in the HLA-A2 positive, which I said was about 50% of the population... ...in the West, is around 1,000 patients a year, is our estimation. The late line cutaneous population could be 2-4 times that. Right 2,000-4,000 patients a year is the opportunity. Would that be distributed equally over the US and Europe? Probably. It's pretty evenly spread. Okay. Yeah. We didn't talk about this. You just touched upon it, but as far as, uveal melanoma in Europe goes... Yes ...how do you think about the trajectory there versus what you've seen here? The penetration rates in Europe are higher for France and Germany. ...two launched countries right now. Probably 75% penetrated in France and Germany. 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- Okay ...maybe the physicians are connected better. It seems to... We're now 80% first-line patients in France, 70% first-line patients in Germany. Really good inroads in both- ...those countries. duration of therapy continues to extend in both. We did see 20% growth in Q1, in both those countries. Mm-hmm. As you look to cutaneous, 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. going back again to uveal melanoma. I think I forgot to ask you whether the non-metastatic opportunity would be attractive because doctors have talked about that. Yeah. What's interesting about uveal is there's a couple of chromosome, mutations. ...that predict, highly predict metastasis. If you have, one or both of those mutations, you're likely to metastasize. The adjuvant therapy is really interesting to us. Yeah. 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. Yeah. yes, we're thinking about how to. Would you need a study for that? Yes. Could doctors just. No, you would. use it off-label. You would need a study. Okay. We're doing a study in, investigator-sponsored study in the UK that tracks circulating tumor DNA, so before metastasis. Once you see an increase in circulating tumor DNA, then you would get KIMMTRAK. That's a pretty novel approach that the investigator was interested in, and we were interested in. We're funding that. We're looking at other ways to fund adjuvant studies. How much would that increase your opportunity in uveal if you were to expand into non-metastatic? Yeah, that's a great question. I mean, most of the patients, unfortunately, are gonna metastasize- ...ultimately. 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? Oh, do you think? progressing into We would think so. I mean, we would think. Yeah it would be a great inhibitor of micro-metastasis. Right. That would seem to be value add. Absolutely. Okay. Maybe let's move on to PRAME. Yep. Can you give us a more detailed overview of that program, what it is? Yeah ... and what indications you feel it could be potentially meaningful to pursue? Yeah. PRAME is highly prevalent. It's a cancer-testis antigen. It's a intracellular protein that is a negative prognostic marker for many tumor types. The tumor cells hijack the protein PRAME to live longer, and to expand. PRAME is only presented in cancer cells, so it makes it an ideal target. We think we've found the right peptide to target. on the cell surface. In our data that we shared at ESMO, would coincide with that in uveal patients, that we had a 50% response rate. In cutaneous patients, we had a 33% response rate, and a couple other patients that were pretty near partial responses. In ovarian, a 50% response rate. In the 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 months. 'Cause these were really late-line patients. 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. Not only do we have an A02 allele that we mentioned is 40%-50% of the Western population, we also have an A24 allele for PRAME that is gonna be in the clinic next year. That is more than 60% of the Japanese population is A24, and another 15% of the West is A24. In Japan, if you put A02 and A24 together, it's about 80% of the Japanese population. About 60% of the Western population with A24. Thirdly, we think that, we wanna explore the half-life, 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. That redosing, we think, is really important for durability over time and bringing fresh T-cell, CD4 and CD8 T-cells in the tumor microenvironment. We do wanna explore what a half-life extended version may bring. We have one of those in the clinic next year as well. Okay. Maybe let's back up a little bit on data for PRAME. 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. Just to remind everybody, can you give us a summary of what you had shown? Yes. Yeah, no, I think it was really informative for us to see the responses that we did given the high prevalence for PRAME. When you do have the PRAME protein, you generally have a high H score. So our median H score is we're in the 180s for PRAME, whereas for a molecule or for a protein like MAGE. a MAGE program, the median H score was below 50. 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 dataset that we had at ESMO, we did have those responses that I mentioned. I think there was some speculation that we'd have lung data- ...lung responses, that was really stock speculation, I think. We didn't infer that we were gonna have that. It's still early. It's phase I data. After that initial week or two, the stock seemed to rebound really well and based on people going through the data. Yeah. What did you learn specifically about non-small cell lung? I think it seemed that the reason people were particularly excited is because of the large indication. It's prevalent. Yeah. Yeah. What did you learn from that initial cut of data that-? Yes ...that you saw and you're obviously now taking action based on what you saw there. Yeah. You can talk about that study. Yeah. What we learned was that these patients, as I said, were only on therapy for a mean of two months. ...which isn't, 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 six different studies that show that if you have a 50% reduction of circulating tumor DNA, that portends well for survival benefit. That gives us reason to believe. We do need to get earlier line patients with that are immune fit in lung. 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. Working with physicians to enroll healthier lung patients. Is there heterogeneity in the lung cancer population that can, you know, preclude getting a clear signal? There is a heterogeneity in lung. There's obviously PDL1 low and PDL1 high. We know Is there PRAME low and PRAME high as well? It's not clear if there's PRAME low and PRAME high right now. We published the H scores of the four patients, they were in line with. ...the other H scores that we have seen. What we do know is regardless of PDL1 expression for KIMMTRAK and PRAME, they were different to PDL1 expression or tumor mutational burden. We would assume that we're indifferent to other mutations as well, but the data will- ...we'll see the data. I think what the heterogeneity will help us with is really the development plan on how will we get to market quickest. Yeah. Where do we develop this given response rates in PDL1 high versus PDL1 low? Right. I think that will help us identify the right path forward. What is the entry criteria for the non-small cell study? It's all comers. Okay. Yeah. we, can stratify them. Yeah ...H score subsequently. We also have the combination therapies open. As I mentioned, PRAME, we wanna move early. Yeah. We have chemo combinations open. We have PD-1 combinations open, and we have a KIMMTRAK and PRAME together combination open. That's pretty interesting for melanoma patients and uveal patients. 2 unique targets could be really interesting together. How is that enrollment progressing? All seven of those, what I just mentioned are enrolling currently. cutaneous, ovarian, lung-. ...endometrial, all the patients. I would say because of KIMMTRAK's experience in having more melanoma relationships- ...melanoma probably the largest enroller. Yeah. In ovarian we saw responses in MAGE, in ovarian. We saw responses 50% to A24 in PRAME phase I with ovarian, so that probably second. Then endometrial and lung, we need to get with those physicians and we have those sites open now. Okay enroll those patients. I mean, as long as somebody has this PRAME mutation, what does it matter what type of tumor it is? Shouldn't it just work across all tumor types? That's right. As long as you have PRAME protein present- Right ...that your tumor cell is using. ...advance, then yes, it should be indifferent. We should be indifferent- Right in theory. Yeah. Could it take different times to see the effects though, depending on tumor? we haven't seen that yet. Okay. Yeah. Because I think some, someone had suggested perhaps that a signal was seen immediately for melanoma, and because you didn't necessarily see a signal right away for non-small cell lung, that perhaps, you know, for some reason, depending on the tumor type, it could take longer to see an effect. Yeah. I think the N is really small for lung. Yeah. It was, you know, three or four- Okay depending on how you count. Where melanoma, we had more patients. Sure ...to evaluate. If we fast-forward to next year, what type of data will you expect to show at the top line for that study that you just talked about? Yeah. We're focused on showing monotherapy data. The combinations are more for safety to be able to move to first line. ...rather than efficacy. We'll obviously have efficacy, but you're not gonna get a clear signal unless you have monotherapy data. That's what we had with KIMMTRAK, and that's what we had early with PRAME. We're focused on that monotherapy. I think we haven't decided how to present the data yet, but we do present data almost only at medical conferences. Right. I could envision a melanoma readout at one conference and then maybe an ovarian at another. Et cetera, but we haven't decided yet. Okay. How big are each of those potential indications that you're looking at? How many patients? Yeah. For PRAME in HLA-A02 positive, in those four, it's about 100,000. Okay. It's meaningful ...patients a year. It's meaningful versus the 1,000. Yeah for uveal. Yeah. Yes. If you do find success in those bigger indications, what would you need to do to your commercial structure in order to accommodate any such launch? I think, to be determined. I think, it depends how broad we can move PRAME and how early we can move PRAME. melanoma obviously we have relationships. ovarian. Melanoma in late line and ovarian in late line post-platinum chemotherapy is about 10,000 patients. Each are about 10,000 patients a year. We'd need to increase. We're very focused on thinking about how to design pivotal trials for melanoma, for ovarian, for lung, once we see signals. Lung is obviously a large population. Yeah. Depending on what that trial design looks like, we would be open to partners, if they could accelerate our time to market and accelerate the value for patients. I guess in general, what's been your inbound interest on ImmTAC just based on the data that you've presented so far? There's a lot of interest in PRAME as a target. Yeah. Is it agnostic to indication? That's a great question. The direction that solid tumor therapies are going- is earlier and earlier. Interest in adjuvant Yeah First line in adjuvant is the interest. Sure. Yes. I did wanna ask you, is there overlap in population that expresses HLA class II GP100 and HLA class II PRAME? yes. How much of that? Significant. Yeah. Both are 90% presented. Okay. it's, you know, 990 by... 9 by 9 is- Yeah. Okay. 80 probably. It might be, it might be identical. It might be close. That's what makes the KIMMTRAK target is targeting melanocytes that then metastasize to the liver. PRAME is a cancer-test antigens. That's why we think together both could be really interesting- Right for, PRAME's RECIST response in 50% in uveal. Yeah. Yeah. Ones that's off well, we're using them together. I think so. If next year you have this update on these, various solid tumor types in PRAME, would you then make a decision right away on which ones you'd wanna pursue? Theoretically, as we've discussed, it should work in all of them. Yeah, we're already thinking about it now. We don't have to wait to present the data- to, think through and design trials for pivotal trials. We'll do that in real time as we see the data. Okay. As you think about, you know, well, let's talk about your cash position. How much do you have, and how much of the potential move forward could that position support? Yeah, great question. We have $417 million we reported this morning. of cash. Our cash balance has increased each of the last several quarters. The, as we said, the sales on an annual basis is around $200 million net right now before growth in Europe. Yeah Hopefully more growth in the United States. The earnings we had this morning, our second quarter, expenses were about $70 million for SG&A and development expenses, so just slightly cash negative. The $400 million is enough for at least the next three years to start two large pivotal trials in PRAME. Right. We're in great shape from that perspective. Cash is not slowing us down. Right as fast as we can in developing PRAME. You have a lot of programs that you wanna move forward into the clinic. What's your view on business development? Meaning wanting to look outside to bring some things in that could be complementary to what you're doing internally. We're very interested and spend a lot of time looking at complementary mechanisms or complementary targeting. We have a research collaboration we announced with Gadeta. Gadeta has a cell therapy for gamma delta T cells, which are universal. They're not HLA restricted, and they have a target that is unique to colorectal and they don't have a bispecific engineering capability. They said, "Hey, let's do a research partnership. Do you wanna try to design a bispecific with this target?" We said, "Yes, that'd be really interesting. By making it a bispecific and adding our CD3, you make it polyclonal. You take something that was gamma delta specific, and gamma delta is a small fraction of T cells. Now you can attract all CD4 and CD8 T cells, so it doesn't matter that it's gamma delta. Gamma delta is the targeting end. Right. The CD3, that we have, makes it, potent. That's a theory. That's one example of what we're doing. Yeah. We're looking for more of those opportunities. Are there specific modalities that you think are particularly complementary to what you have in-house? I mean, we're experts at protein engineering. affinity maturing and affinity-enhancing these bispecifics. Could you do ADCs? We could, in theory, take the bispecific targeting end and add an ADC. In theory. We thought about it. Yeah. There's different ways to potentially do that. How does the tox profile come into play before you make a decision like that? 'Cause you already know ADCs are toxic in general. Yeah. given how specific our targeting ends are- for, the targets, it's probably gonna be the cleanest. It would probably... Right? Given- Yeah These are super low doses that we're giving. We're giving in KIMMTRAK, it's 68 micrograms weekly. Yeah Because it's so specific for the target. We'd have to explore that. The reason we're so excited about the autoimmune platform is because we can design the targeting end- Right to be specific for exactly the cell. Right that's causing the autoimmune issue. For type 1 diabetes, for example. Right. Right. pancreatic beta cells. Right? Can you combine the bispecific with the PD-1 and down-regulate the immune response? Right -on a tissue basis. On a cell or tissue basis, and not have a systemic therapy? That's really cool. Yeah. That would also allow you to move out beyond oncology. Yeah. That's how we think. Autoimmune is huge. Especially lately. Yes, definitely lately. With that, we're almost out of time, so I think we'll stop the conversation here. Brian, thanks so much for making the trip out. We really appreciate it. thanks everybody for joining us. Hope you enjoy the rest of the day. Thanks for having us.