Immunocore Holdings Plc Q2 FY2023 earnings call

• Commercial: KIMMTRAK had its strongest revenue quarter-to-date in Q2 with $57.8 million in net sales, up 11% quarter-over-quarter. Launched in four additional markets, including Italy, and reached a better-than-expected reimbursement agreement with Germany.
• R&D: Making progress in oncology and infectious disease pipelines. Starting the first Phase 3 randomized trial with PRAME-targeted ImmTAC. Ongoing trials in infectious diseases investigating functional cure for HIV and HBV.
• Financial: Q2 net loss was approximately $18 million. Cash position remained strong at $435 million, driven by KIMMTRAK revenue, U.K. tax credits, and disciplined expense management.

In the second quarter, Immunocore's KIMMTRAK revenue was a key segment. Net KIMMTRAK revenue grew to $57.8 million in Q2 from $52 million in Q1, primarily driven by growth in the United States. KIMMTRAK is approved in over 35 countries and has launched in four additional markets this year, including Italy. A reimbursement agreement with Germany was reached, which is slightly improved from accounting assumptions. The revenue contribution of KIMMTRAK is significant to the company's overall financial performance.

• Expect R&D expense to increase gradually as they expand PRAME investment, including the new Phase 3 melanoma trial.
• Aim to launch KIMMTRAK in additional European countries by the end of 2023 and achieve reimbursement in France in 2024.
• Plan to submit three INDs or CTAs for new oncology products by year-end.

• Reimbursement challenges in some markets, such as the U.K. where innovative products often face negative funding decisions from NICE and extended processes.
• Uncertainties in clinical trial outcomes, particularly for infectious disease candidates where there's no prior established functional cure for HIV.

Q: Good morning. Thanks and congrats on the progress and congrats on Phase 3 PRAME program. I guess keep my one question to PRAME. David, can you just talk a little bit about your plan to start the Phase 3 in melanoma? I know you gave an update on the ESMO data and the duration. I think I just saw the curves. And how much of the ongoing expansion cohort data played a role on that. Are you seeing similar response rates? I think you had 33%. Are you seeing same number of patients? Just talk a little bit about the totality of that, particularly in the expansion that you were seeing going on now? And then as a follow-up to that, you did comment that you're thinking about the next tumor type, can you just talk a little bit about what you're looking at and what you're seeing in front of you in ovarian and maybe lung cancer for PRAME?

A: Yes. Sure. So two questions. So number one, Michael, again, we looked at the ESMO data, which we showed a very promising update in terms of durability. We're enrolling the expansion, although it's still early, we looked at this data. And in a - from a general drug development point of view, I won't speak specifically to the data, which we'll share next year. But from a general drug development point of view, Michael, we ask two questions. What are the percent of patients that are benefiting? And can the treatment effect in that population support the primary endpoint we're interested in, in this case, PFS? For us, it was clearly yes, based on that data plus the original ESMO. We took that to the FDA who agreed with us when they reviewed the data. We shared that data with global KOLs and so, I think it became clear to us and everyone who sought to move forward with the Phase 3 study. With regard to the other tumor types, we saw the activity in ovarian, which triggered us to do that expansion. That's still ongoing. We are very interested, of course, in lung and endometrial as well. So those expansions are still ongoing, and I think more to come on that as we review the data.

Q: Hi guys, good morning. Congrats on the strong KIMMTRAK quarter, and it's exciting to see all the new updates. Just a follow-up on PRAME and the cutaneous durability update. So clearly, the initial response rate is higher than KIMMTRAK, but again, just to follow up on durability. How confident are you that the durability you are seeing with PRAME, even though it's early, is what you saw with KIMMTRAK? And I guess the same question just asked another way, based on the PRAME construct and design relative to KIMMTRAK when you consider TCR and CD3 potency, is there any reason why you wouldn't see similar durability?

A: Tyler, so the only direct comparison we can do, and it's limited is in the uveal melanoma because that's where KIMMTRAK monotherapy has been mostly dosed and where we have PRAME data. And we have the three PRs with durations of 12-month, 16-plus and 17 months on PRAME. In the Phase 3 KIMMTRAK study, the median duration of response was 11 months. So that's Phase 3, and this is Phase 1. But I think the data for PRAME is very promising in terms of tolerability. In terms of differences between the molecules, I think that was your second question. The TCR end has the same picomolar potency, the CD3 end is the same. The peptide density for PRAME is higher than it is for gp100, but that's essentially what we know right now.

Q: Thanks for taking the question. Maybe for David, can you just walk us through - obviously, you're moving forward PRAME here in the first line versus KIMMTRAK in - and second and third in cutaneous melanoma. Can you just walk us through just the numbers for the accessible market for gp100 versus PRAME and cutaneous.

A: Yes, Justin. So the current Phase 2/3 study TEBE-AM and KIMMTRAK, we estimate to be 2,000 to 4,000 patients per year, and that patients have progressed on ipilimumab and BRAF-targeted therapy and anti-PD-1s. For PRAME in first-line, part of the reason we're so excited about this, the opportunity is greater than 10,000 patients per year. That's the difference in terms of size.

Q: Thank you and good morning. Congrats on the progress from me as well. A lot of questions on PRAME, but I would just want to focus on KIMMTRAK and the cutaneous melanoma opportunity. Well, actually, uveal, I know that there's been developments on the competitive landscape, and I know that there are thoughts around potentially combining KIMMTRAK with PRAME. So can you just give us your overall strategy there in uveal melanoma?

A: Yes, I'm happy to take that and invite anyone else to join also. So KIMMTRAK had a great survival benefit and there's a lot of patients who benefit. We are really excited about our combination of KIMMTRAK plus PRAME. It's - we're currently doing the dose escalation optimization. They're both very active drugs and the idea there would be to study KIMMTRAK plus PRAME in the first-line setting. So once we have that data available and we can have a good regimen, we'll be able to share that data.

Q: Hi. Good morning and thanks for taking the question. Maybe just to pivot a little bit to the HIV program. We're hearing a lot more interest in sort of the program as we see potential data near term. Can you just frame for us how we should expect the initial data cut to look? And what exactly is the expectation for patients who withdraw ART over a 12-week time frame?

A: Thanks. David, you are - Yes, I'm happy to take that. So in terms of the data, we were doing the multiple ascending dose where we treat patients for 12 weeks with intra-patient escalation and then at a target dose. We expect to have multiple cohorts completed, multiple-dose escalations completed when we share the data. The data will include, of course, safety and biomarkers during the initial 12-week run in. After 12 weeks, we will interrupt both our bispecific as well as the antiretroviral therapy, and there we'll look for a rebound of the virus. Historically, I think the virus will rebound usually within a few weeks. I think most of the patients usually rebound within four weeks. We have a 12-week planned interruption. And so, in terms of what we're looking for there, it's a new field. I mean no one has ever really had a functional care in HIV. So we're really excited to see where this data leads us.

Q: Hi guys. Good morning and thanks for taking my question. I had a question going back to the planned Phase 3 study for PRAME and melanoma. So it sounds like the decision to go into first line was driven partially by the KIMMTRAK ctDNA data. And so I was just wondering about the concept, why the activity on ctDNA was higher in first-line patients and whether that is something that would be the case for other tumor types as well.

A: Yes. I'm happy to start. So the data was based on the ctDNA, but also based on the survival and first line is better. I think we have two hypotheses, the first is that perhaps newly diagnosed first-line patients have a better immune fitness. And the second hypothesis is that the patient's tumors might not have been edited as much in contrast to after anti-PD-1. So that's a pretty standard phenomena, by the way, for all immunotherapies. And so we do expect - I mean, we haven't treated first-line patients, but we do expect that the activity will be larger in the first line for cutaneous as well.

Q: Thanks and good morning, good afternoon, and congrats on all the progress here. Just a follow-up question on the Phase 2/3 trial with KIMMTRAK in second-line or later cutaneous melanoma. With the randomization of Phase 3 portion to commence immediately following completion of accrual into a Phase 2 portion, I'm wondering if you can discuss how efficacy from the Phase 2 portion might inform changes to the Phase 3 design. What changes could you implement? Would there be potentially accelerated pathway depending on what you see in that Phase 2 portion of the study?

A: Yes, Patrick, that's a great question. And we specifically spent a lot of time designing this seamless Phase 2/3. So what we'll look at in the Phase 2 is, number one, we have a KIMMTRAK monotherapy, we have a KIMMTRAK-plus pembrolizumab. Do we need to have the pembrolizumab on board, yes or not. So we can decide to discontinue one of those arms. Number two, we'll be looking at the treatment effect relative to the control arm because we may need - may be clear that we can decrease the size of the trial if the treatment effect is larger.

Q: Good morning. Congratulations on the progress and thanks for taking my questions. Two on our side. First one is on the cutaneous melanoma. Could you elaborate more on the less frequent dosing? What led you to take that leap and is it only driven by KIMMTRAK or is it driven by the Phase 2 data you got from the PRAME program?

A: Yes, I'm happy to do that. So there's a couple of things that led us to the dosing. Number one was we talked about the KIMMTRAK experience. Number two is if you look at the - if you look at the Kaplan-Meier curves for first-line PD-1s, including nivolumab, you see that most of the progression - in fact, the majority, 2/3 of progressions occur during the first 12 weeks. So that's where we plan to have the weekly dosing because that's where the trial PFS is one and last. After 12 weeks, the Kaplan-Meier curves really plateau out. And so, we didn't think you need to have a weekly dosing regimen after 12 weeks. And then, of course, by one year, it moves to a once-monthly regimen. And then I think just finally one other point. When we look at the PRAME data, but also KIMMTRAK we see the majority of the tumor shrinkage occurs in the first 12 weeks. So that's the time to have the weekly dosing.

Q: Hi, good morning. This is [Jay] on for Peter. Thanks for taking our question. I just want to get a little more color around the organic growth for the second quarter for KIMMTRAK? And if you could give any - talk to the volume of - volume growth versus price growth? And any one-timers we should be thinking about here stocking orders and pricing benefits for U.S. versus ex- U.S.?

A: Thank you for that question. So most of the growth was driven from the U.S. with the 14% quarter-over-quarter growth. That was pure demand growth. We did not see any difference in patterns of stocking per se. And you have to consider that we took a price increase at the beginning of the year in January of 2.5%.

Q: Hi, there. It's Nick on for Rajan. And thanks for taking my questions. If we could just come back to the PRISM trial and the design there. I was just wondering what the rationale was for the selection of the two doses, they seem to - or at least optically, they look quite far apart. Is - why was there not a dose in between? Is that something that you've agreed with the FDA? And then looking further ahead, could you just give us an idea of what you see as the bar for efficacy and what good data would delight you.

A: Yes. So with the selection of the two doses, we had multiple doses that were active and well tolerated in Phase 1. In fact, we had a sevenfold dose range. We have 20 micrograms all the way up to 160 micrograms. And we chose the 160 originally based on modeling and simulation, although we had fewer patients at the lower doses. And I think that was the reason for the need to explore a lower dose. When it came to the selection of the lower dose, we had two choices, 20 or 40. 20 was the threshold dose and we felt just in general, a good drug development never to choose the lowest dose because of variability in PK, you'll end up with some patients having too low of exposure. And so, that really set us on choice of 40. With regard to the bar for efficacy, the nivolumab median PFS has really ranged, I think, between 4.7 months to, I think, 8 months. The most recent RELATIVITY-047 was 4.7 months from a median perspective, we're going to have a blended median PFS because we'll have some patients who are on Opdualag or some patients who are on nivo, but I think that the median PFS blended is probably still going to be less than 8 months. It just will depend on how many patients are randomized to the Opdualag.

Q: Thanks for taking my question. How is enrollment going for the PRAME, A02 trial? And what should we expect to see in the first half '24 data?

A: Great. Mohamed, do you want to take that? Sure. As we had said earlier, we have moved from a Phase 1 footing to a Phase 2 footing. So we continue to open up additional sites and continue to accrue to our multiple priority expansion cohorts as well as the standard of care combination. So all of that continues to go according to plan. And as we've said, we plan to share the data as it matures in the first half of next year?

Q: Good morning, everyone, and thanks for taking our question. So this is a bit of a hypothetical at this point, but it'd be interesting to see kind of what you expected the play would be between the PRAME agent and the KIMMTRAK agent in cutaneous melanoma. When you did previously PRAME post KIMMTRAK data and it suggested there was a ton of activity, but what happens the other way around?

A: Yes. So in cutaneous mel - so the PRAME after KIMMTRAK was in uveal and although we didn't see RECIST part response was really remarkable, the disease stabilization that we saw there. Now why was it disease stabilization and not RECIST partial responses like we saw in first line? We don't know that. We can speculate, but we don't know. I think we really are excited to study PRAME plus KIMMTRAK to understand how our platform works when you do multiple combinations. It makes sense to study it initially in uveal melanoma because we have a lot of KIMMTRAK experience there. But I think clearly, cutaneous melanoma would be the next step. I think there are two ways to think about it, Gil. One is because both PRAME and gp100 are broadly expressed, we could target more cells within the tumor. And you could also think for cells that co-express both, there might be more peptide HLA targets on the cell for the T cell to kill. So I think both of those are active hypotheses.