Immunocore Holdings plc (IMCR) Earnings Call Transcript & Summary

Thank you so much. Welcome to Barclays Healthcare Conference -- Global Healthcare Conference in Miami and do e-mail us or reach us on Bloomberg, if you have any questions, I can get them message to me. My name is Peter Lawson. I'm one of the SMID Cap Biotech Analyst at Barclays and focused on oncology-related companies and really delighted to have up on stage with me management from Immunocore. We have Brian Di Donato, CFO; and David Berman, Head of R&D.

And I guess my first question really going to be around, I guess, revenue growth and kind of how we should be thinking about it? You've done a fantastic job with over the last 3, 4 quarters on accelerated growth. How long does that story continue for? And what are the pushes and takes that we should be thinking about as we enter 2023.

Yes, Peter, first, thanks for having us here. It's been a pleasure. And we -- as we mentioned in earnings about 10 days ago now or 2 weeks ago now, that we're really pleased with the $140 million -- $141 million in net sales that we had in 2023 for -- sorry, 2022 for a partial year, and we have several growth drivers as we move into 2023. Number one is Europe. We expect to have another major European country reimbursement agreement by midyear and probably 5 smaller European countries in the second half into year-end. So that's really the growth drivers. Right now, we have revenue from U.S., France and Germany. So those additions will be meaningful as we move throughout the year. The U.S., we're about 50% penetrated in the U.S. right now, but more to do in terms of moving to the community. So really good penetration in our academic centers, but more inroads to make in the United States.

Got you. And so with the community settings, I guess that kind of just drives the slowing of revenues in the U.S. at least as you kind of penetrate smaller and smaller accounts.

Yes, that's what we think. The community melanoma physicians, oncologists may have 1 patient or 2 patients a year with metastatic uveal melanoma. So it is more labor intensive to make sure that they're informed and to get out into the community for growth. So yes, it could mean slower growth in the United States in 2023.

Does that incorporate kind of a switching strategy? Does it become more online-based or -- versus in-person.

No, it is still in-person. We do have a marketing effort in the United States to reach more physicians but it still requires a person-to-person interaction. So we're setting ourselves up for that as well.

Okay. And where do you think it caps out what percentage of uveal melanoma patients will eventually see KIMMTRAK?

Yes. So in France and Germany, we have great penetration. We estimate that we're 75% to 80% penetrated in France and Germany. The early access programs really helped to launch KIMMTRAK in metastatic uveal melanoma for A02 positive patients. The U.S., we don't know. The U.S., where we think we're 40 -- 50% penetrated, but too early to tell what the ultimate penetration will be.

How do we think about other -- developing other alleles for KIMMTRAK, so beyond AO2.

Yes. So for metastatic uveal, it tends to be a Western disease and so AO2 makes the most sense. For PRAME, PRAME having multiple indications such as lung, ovarian, endometrial. We have announced another [ allele ] A24. A24 adds about 30% to our A02 patient population. A24 is more than 50%. Japan is A24. So in Japan, A24 and A02 together are about 80% of the population. So that's really exciting as we move into clinical development in Japan. And then in the U.S. and the Western Europe, AO2 is about 40% to 50%, depending on the indication. And then A24 adds about another 15% to 20%. So we're about 60% covered with those 2 alleles alone. And then we'll continue to look at other alleles in our development pipeline.

And so for uveal melanoma, there is no benefit to add that additional allele A02 or is it just...

So it will be nice to have PRAME and A24. So we have shown that PRAME has efficacy in uveal as well as cutaneous melanoma in some small patient numbers, we did see a 50% response rate with PRAME in uveal. So the A24 allele could add something for those uveal patients at some point.

Got you. So there's kind of no further development around gp100, you kind of take it from the PRAME side for uveal melanoma.

Exactly.

And the overlap of PRAME, and I know it's probably been asked more times today and tomorrow, but the overlap of gp100 and PRAME. Could you remind us, especially in uveal melanoma.

Yes. Do you want to?

Yes. So in uveal melanoma and cutaneous PRAME is expressed in a majority of the patients as is gp100. So there's probably a very big overlap between the 2. But I think between the 2, there's probably complete coverage of the melanoma just given that both are very high frequency expression.

Got you. And then I know on the earnings call, you mentioned there is kind of approaching 9 months for duration of treatment. How close are you to 9 months? And I guess, what does that mean?

Yes, in the real world, we're pretty close to 9 months. We saw both in our Phase II, which was a second line and our Phase III, which is first line that the duration of therapy was around 9 months. And we'll give an update on the Phase III study later this year. And what we're seeing in the real world, we've only been -- we're only about a year into the launch now, but the duration of therapy is right about that -- approaching that 9 months. It's too early to tell. People ask, will it be longer than 9 months. Too early to tell. Later this year, we'll have a better read if it could be longer than 9 months.

Okay. And so is there anything else we should be thinking about for whether it's duration of treatment or kind of how you tackle first line versus second line in uveal melanoma?

No, I think you're thinking about it the right way. We're more than 50% first-line therapy now. The -- we know from the subgroup analysis in the Phase III that the smaller the tumor burden that the hazard ratio is even lower. The hazard ratio is 0.36 versus 0.51 for the overall Phase III study. if you had tumors less than 3 centimeters. So getting patients treated early is important where you're thinking about it the right way.

Got you. And physicians treatment beyond progression, is there any benefit for doing that?

Absolutely. Yes, absolutely. It's in the label in Europe. It's in the U.S. It has referred to the Phase III trial, which in the Phase III trial, 44% of the patients were treated on average of 8 weeks beyond progression. Absolutely. We showed progression analysis that shows treating beyond progression adds to the overall survival. So it's very important to the survival benefit.

Okay. And that doesn't need any, I don't know, additional coaching, it's kind of well understood.

It's well understood that the academic centers who participate in the Phase III. It does require some coaching in the community as well.

Okay. And so you're in that first experience, I guess, in the U.S. in that community. And how is that kind of being received to treat beyond progression?

Yes, so far so good. It's a work in progress, but, yes.

And I guess there's a relatively easy sell because there's nothing else taken that these patients can move on to a [indiscernible] chemotherapy?

Yes. And I think the data speaks for itself that it is -- it adds significantly the survival benefit by treating beyond progression and there's something else going on with the mechanism.

Got you. And then, I guess, competition in that space IDEAYA what is it, the PKC inhibitor, how does that kind of make you change your tact or approach in that space?

Yes. So it's -- so they've shown responses in metastatic uveal melanoma. It's good for patients, of course. They've announced that their program is going to focus on the HLA-A2 negative population. And they'll do a medical practice informing study in the positive. So I don't think that they'll end up with a label in the positive. For us, it doesn't change anything. We're interested in combining PRAME plus KIMMTRAK because PRAME had a 50% response rate in uveal melanoma as a monotherapy. So we think that 50% response rate of PRAME on top of the hazard ratio of 0.51 survival benefit for KIMMTRAK could be a really powerful combination. So that's where we're focused.

And you're distinctly thinking about combining as opposed to using them serially?

Yes, because we showed that you get much for PRAME much greater activity to use it in first-line compared to if you use it after KIMMTRAK.

Okay. And so for you, that drives deeper or faster responses. So...

Yes. So one of the interesting things that, as you know, Peter, with KIMMTRAK is, there was a very modest response rate, but an incredible hazard ratio survival of 0.51. And the question, was this disconnect going to be seen with PRAME and with other programs or was it gp100 uveal melanoma. So we now know that it's probably -- it's gp100 specific because with PRAME, we do see a high resist response rate in uveal melanoma, so an apples-to-apples comparison. So a majority of patients probably are benefiting from KIMMTRAK. It's just not apparent in radiographic tumor shrinkage. With PRAME it's the opposite, we do see dramatic tumor shrinkage. So that's why I think the combination would be very interesting in melanoma.

Got you. Okay. For the KIMMTRAK in advanced melanoma kind of, when do we see data around there?

So that study is a 3-arm trial, KIMMTRAK plus an anti-PD1 and then a control arm. The study is just starting. And the idea is that we'll have the Phase II portion completed enrollment randomization in the middle of next year. And then we have a dual primary endpoint of ctDNA reduction and survival. The survival won't be fully mature, but the ctDNA will be mature in the second half of next year. So we will look at ctDNA and we'll look at survival. And so that data, hopefully, will be available in the second half of next year. And we'll present that at Congress. But that information will inform what changes we need to do to the Phase III part of that study.

Okay. And what changes would you envision?

So one is we could drop one of the arms, perhaps the anti-PD1 is not needed. If the efficacy is the same, we'd prefer a monotherapy approach. If the estimated hazard ratio is larger, is more striking than a hazard ratio of 0.7, we could shorten -- we could decrease the sample size, shorten the trial, the Phase III part. We could power it for a more aggressive hazard ratio.

Interesting. Okay. PRAME. I'd love to move on to that, if possible. So just kind of or the differentiation of your PRAME approach there, multiple people have tried to target PRAME. What gives you kind of a better shot at PRAME?

Compared to other approaches?

Yes.

Yes. So it's nice to see that 2 different approaches are showing responses, both the TCRT against PRAME in solid tumors and then our off-the-shelf PRAME. With our PRAME, I think with our TCR bispecific, we're very pleased to see the durability of responses. I think that's the major -- that's one of the major benefits. And it's that consistency we see throughout our platform from KIMMTRAK to MAGE and now PRAME, we see responses lasting out months. And I think it's still a question mark on the TCRT approach, whether you can get that level of durability. I think the other benefit of our approach is it's a very predictable safety profile. The key AE we see a cytokine release syndrome. And that's seen within the first 1 or 2 doses, and in fact, hours after the first couple of doses. So it's a very predictable and manageable safety profile. So I think it's potential to be a very good benefit risk profile.

And so the CRS profile, does that require you think hospitalization or...

So we -- yes. The -- I mean, currently, it does just because it's a Phase I trial, but it turns out that half of the patients are not having CRS any, and the ones who are most of them are having Grade 1 with a minority having Grade 2. So I think as we move the regimen forward, we can explore whether you need to keep patients overnight or not.

Okay. in any way you could that restrict its use outside academic centers? Is that worry in any way?

Well, with KIMMTRAK, we're seeing even now, even though KIMMTRAK is a higher rate of CRS, it's about 80%. Half of that is Grade 2, half of it is Grade 1. We're seeing some use in the community. It requires education, but I think with PRAME, it's an even more gentler safety profile. So I think it will have broader applicability in the community than KIMMTRAK.

Got you. What do patients do in the community setting, where do they go start development CRS or they kind of with the physician at the time of injection...

So for KIMMTRAK and for the clinical trials on PRAME, we monitor them overnight on the doses that are likely to get CRS, which is the first couple. And so there is no CRS that develops outside of the monitoring period. And for both KIMMTRAK and for PRAME, when they do develop it, it's actually quite -- it's managed very predictably mostly with just fluids sometimes supplemental oxygen. Occasionally, a single dose of steroids is all you need. So it can be managed in a routine setting, it's nothing, I think, too out of the ordinary.

Do you have to be careful about how you expand in the community setting, so there's a hospital close by or...

I think if we do move to complete outpatient dosing, there probably will be some type of patient leaves with it, you have to be near an emergency room. But the good news for our platform is that the CRS is very predictable. Some of the doctors say you can almost set your watch to it. So you know if they don't develop a fever in a certain period of time, they're really unlikely to develop CRS.

Could you remind me again, what's the period or time?

It's usually about 8 hours.

And only for the first 3 doses.

Yes, only for the first 3 doses and that tends to decrease with each subsequent dose. There's a tachyphylaxis of CRS.

Got you. Okay. For PRAME, kind of which indications do you think have the highest probability of success or -- and then kind of how do you marry that with opportunity and unmet medical need?

So we saw really nice activity in melanoma and ovarian cancer. And so it made sense to initiate expansions there. Endometrial, it made sense, not because we saw clinical activity, but endometrial has very high expression of PRAME. So in theory, it should work in endometrial. And then in lung cancer, we did see ctDNA reductions, which is, to me, a measure of something is going on, and it justified expanding further to try study lung cancer, which is a very heterogeneous disease. So we need to study lung cancer to better identify where these signals are. In each of these 4 indications, there is still an unmet need. And so the initial approach is to identify signals of activity and then either move earlier or based on the signal of activity, do we have a potential for an accelerated approval. I think that's what we're going to find out with these expansions.

Okay. So moving forward for each indication is going to clearly vary based upon those signals where they get accelerated.

Yes. So do we see resist responses, do we see progression-free survival? Is it -- yes, those are the questions we need to ask. And those are the questions that we're asking now.

And you're expecting to see single-agent activity or would you want to combine to be able to...

Yes. So we definitely expect to see signal-agent activity. That's what we saw with KIMMTRAK. We saw that with MAGE, we see that with PRAME. We see it with PRAME in uveal melanoma, in cutaneous melanoma after checkpoint failure. We see it monotherapy activity in ovarian cancer after platinum. So we see it in a variety of different tumors. So there's no doubt that we should see monotherapy activity. I think combinations do make sense, both strategically because we want to move upfront and then you need to combine, but I think also, if you think of the checkpoint field, the anti-PD1 had about a 19% response rate in third-line lung cancers monotherapy. It's only when they move to first line and combined with chemotherapy that you start to see a broader higher response rate and activity. So I think there is a principle of monotherapy activity and rationale for combinations.

Got you. Okay. So what long ovarian -- endometrial, I guess, that we didn't see the responses.

But it makes scientific sense to study.

And is that a case where you could see long stable disease and...

Potentially, yes. Yes.

But then I guess in presumably in long, it's difficult to persuade physicians or patients to stay on.

Right. We would like to see tumor reductions and partial responses and we have no reason to think we shouldn't see it. It's -- I think it's about identifying the right population.

For the endometrial, would you think about like a maintenance setting?

Yes. For ovarian, we would think about a maintenance setting. I think for endometrial, we hope to move up into earlier line of therapy in combination. But with ovarian, the paradigm is set for long-term maintenance type dosing, I think would make sense.

It seems when we speak to physicians, couple at Karyopharm. I'm sort of moving into a maintenance setting in endometrial, you seem pretty receptive to that. Is that something you've kind of discussed?

We haven't discussed it yet. I think we're waiting to see our signal first, but I think anything is potential. I think our regimen is a very well-tolerated regimen with no additive chronic toxicity. So it would will serve very well in a maintenance setting.

It seems ideal from what you saw from your uveal -- an unmet need, and so you can keep patients on for a extended period of time.

And with our dosing, I mean, we think that's actually one of the reasons we get durability because every time we give our dose, we think we bring in fresh new T cells. So it's -- we think that's potentially why we get durability whereas TCRTs you give your one shot of TCRT and it either persists functionally or it doesn't persist. So there is rationale for repeated dosing.

CTDNA reduction. It's been fantastic for what we've seen for earlier studies, do you think that kind of continues to be a predictive value in PRAME?

Yes. So for uveal melanoma, we actually have the Phase III ctDNA reductions coming up at AACR, and it confirms what we saw in the Phase II. So we're quite excited about that. In the other tumors, there have been some studies showing ctDNA reduction correlates with benefits. There's been a friend of cancer research publication in lung cancer, which pool different checkpoints. To me, what I think we're seeing in the 3 patients with lung cancer in our Phase I study who had ctDNA reduction. And looking at the individual mutations as they go down. it says something is going on. It says we are having an effect on some percentage of the tumor. So to me, it just gives confidence that there is activity, and I think we just need to dive a little deeper and look at the right populations, but it says to me there is activity. I think ctDNA is not yet at a regulatory endpoint, which is where you want to eventually end up. But it is in a Phase I setting to me says something is going on.

Got you. And I guess with uveal you are thinking about combination strategies with KIMMTRAK. Can KIMMTRAK -- is that the similar kind of thing happening for cutaneous melanoma as well?

Yes, I think that would make great sense to study in cutaneous melanoma. We, at this point, we're focused our cutaneous melanoma on the PRAME monotherapy and on the Phase III trial. So we're focused on that. But I think eventually, it would make sense definitely to study it in cutaneous, which is, of course, a larger opportunity than uveal.

Got you. And I really shouldn't ask you about the HIV study, and I know that's been getting a lot of questions today.

Yes. So our platform can also be applied to viruses. In fact, I think T cells evolve to recognize viruses. Because we never live long enough to develop cancer. And so we've developed TCRs to recognize an HIV peptide with the goal of functional cure in HIV and for HBV. And what we're really excited about is we presented data at CROI where we completed our single ascending dose study in HIV, patients with HIV who are stable on antiretroviral therapy. These patients have a very low reservoir of T cells that are infected, about one in a million CD4 T cells in their blood. And everything that we predicted we've seen, which is quite remarkable. Number 1 is at the highest dose of 15 micrograms we saw about half of the patients have IL-6 induction in their blood. And the reason this is important is in our cancer trials, we only see IL-6 induction at 15 micrograms in patients whose tumors express the target we're going after. If there's no target, we don't see IL-6. So that gives us hope that we are actually seeing on-target activation. Secondly, we didn't see any lymphocyte trafficking out of the blood at 15 micrograms in all of our oncology programs at that dose, we do. And we think that's because lymphocytes are tracking into the tumor. And third, we didn't see any clinical cytokine release syndrome, no fever at 15 micrograms. In our oncology programs, we always see clinical CRS at 15 micrograms. And the reason we believe is because HIV has a very low antigen burden compared to a big large solid tumor. So everything checks the box in terms of what we want to see. And it would -- HIV for us is like a heme like tumor. It's not a solid because it's infected cells in the blood. The only question mark has been is there enough antigen produced and with peptides presented on the surface that we can actually kill them. The IL-6 induction says yes, but of course, the proof now will come when we start our repeat dosing, and then we're at 12 weeks, we're going to stop the antiretroviral, and we're going to stop our bispecific, and we're going to look to see if we can prevent rebound. So we're quite excited about that, and we hope to share that data by next year.

Perfect. Very well touched. Thank you so much.

Thank you Peter.

Thank you, David.

Thanks a lot.