CureVac N.V. (CVAC) Earnings Call Transcript & Summary

Perfect. Welcome to the afternoon sessions of the BofA Healthcare Conference. So I'm Geoff Meacham, and my colleague, Charlie Yang, is on the stage with me. We're thrilled today to have CureVac and CFO, Pierre Kemula. Welcome. Thank you very much.

Yes.

Yes. So Pierre, maybe just give us a bit of a status update about how mRNA technology, obviously, brand new to the world, come COVID, but now we've seen an evolution of the technology. Give us kind of where you are relative to, say, Moderna or BioNTech and your biggest points of, I would say, differentiation in the technology as a starter?

Sure. So -- and thanks for the question. So we are part of the 3, I would say, large mRNA companies, right? We are fully integrated. We do own technical development of manufacturing and research. We are partnered in vaccine, of course, with GSK, as you know. And we came out with recent data earlier this year, where I think granted its small numbers, Phase 1, both in COVID and in flu, but what we seem to see is that we have very low-dose immune activation, right? We showed that at 2 micrograms -- sorry, it's small, it's 2 [ millionth ] of a gram, we see that we could do better than the existing licensed vaccine in flu, right? And we see that you escalate the dose up to 200 micrograms, we still haven't yet really fully hit the ceiling in terms of reactogenicity, right? So I think this gives us the second-generation backbone a room to play, right, where you want to basically add all these antigens and still remain in a reactogenic profile, which is acceptable, right? So I think this is where we're headed. We announced yesterday that we are starting -- that we have started a flu trial, so back to Phase I, but there was a quite [ relevant ] construct, which is more than 4 antigens, right? So it's what is required by the authorities to have B and A strains. And so we will be testing different constructs at different doses so that we can move into Phase II in the second part of this year.

So the concept, though, is the -- relative to other competitors to have a meaningfully lower dose. And in theory, you could have better tolerability and then you have engagement. I think, when we first hit the IPO, there was questions of interferon, like you engage different parts of the immune system relative to other platforms?

So yes, well, that's the whole idea. So what we've done over the years, right, is really to try and work on the regulatory elements of the UTRs, where the site of the flagging side of the RNA, right? And so we've looked at millions of human mRNAs and looked at why they would be acting differently, whether it's the blood or other tissue. And so we've really looked at what these building blocks is Lego blocks, right? How do we interact, and what do they actually do? And I think we have, in combination with the delivery of the LNP, right, a backbone, which must have very good -- interested in a mechanism that works pretty well at an express -- quite a bit of protein, independent of the dose that you inject, right? It's interesting because we look at the immune response, right, I mean there is a dose response, but it's not super clear. We're in a boosting system, even at 2 micrograms, we do actually quite well. And so that bodes well for stringing up antigens and have a broad vaccine and still, of course, being very much in the limit of reactogenicity, which we know is a key driver for acceptance for vaccines, right?

Right. And I would say, so for COVID, what are the challenges in -- developing today? I mean, obviously, it depends on the strain, and it depends on kind of the cadence, right, of new infections. But also though, maybe help us with like kind of what background of having Moderna or Pfizer, BioNTech experienced patients in the study? How can you tease that out to help maximize your effect size?

Yes. So COVID is a great question, where we all hope that most of the wave is behind us, right? But from a company's perspective, right, like having a backbone approved, right, which is probably the fastest way to get approval, then you can start with the authority, say, well, I just changed the antigen, right? So it's a great advantage of something approved, right? So the other thing is, today, I think if you'd come out with a lower dose and potentially with a better side effect profile, you may have some sales, right? And there's probably a bit of room on the pricing as well. So of course, the big wave is gone. We don't know what the future will hold for us, but at least if we come with a product which is on the efficacy side, but also on the tolerability side, on the right side of things, it's a good way to start having a product down there.

Right. And so you guys use it as a potential source of -- it's essentially a source of capital as opposed to -- and it obviously validates the platform.

So it's a platform for us, capital, too. Specifically, we do that hand-in-hand with GSK, and this is a 50-50 deal, right? But we are capped in our spending at $100 million. And so we will reach this cap in the coming months. And so rest of the costs will be taken over by our partner. So for us pushing that and having an approved product is something that makes sense. Two, I think you want to have flu on one side and then COVID and then you want to have them together, right? So having been there makes a lot of sense.

Yes. No, I think that makes sense. I mean when you think about the regulatory -- like to get there, you have to have data obviously in both of them separately, right? So talk a little bit about kind of the milestones for the COVID program. And then Charlie, maybe we can talk about the flu program.

Sure. So we will move into Phase II. We reported Phase I earlier this year, right, for the COVID program. It will be a Phase II program, where we will have 2 constructs, a monovalent and a bivalent construct, right? Of course, before moving to Phase III, we will see which is the right antigen that we need to encode, whether it's still [ BFI ], right? So we'll be -- so that's the approach. And then, of course, the discussion with the authorities is, what is the approval path? Because we can't do an efficacy study anymore, of course, everybody has been either positive or [ reactive ], so it doesn't work this way. So it would have to be, I guess, a non-inferiority or also immunogenicity landmark to get to. So -- but I think we need to generate that Phase II data, and then we'll discuss with these guys.

Essentially like a booster study.

It's a booster study. Absolutely.

Yes. Okay.

So I guess moving on to flu. Maybe, I guess, just to follow on a similar line of thought like, maybe you can talk about the kind of trial design that you're running? And how we should think about it versus the approved vaccine and -- especially in light of the competitive data set that we have seen so far? What's your expectation? And perhaps what are the next milestones that you'd like to see?

So -- great question. So maybe we have to paddle back a bit for flu because we presented, I think, sexy data earlier in the year, but it was a single-antigen [ CAS ] drug, right? And so of course, now we're starting Phase I again with this multiple antigen, right? So here, we will have multiple arms, right, in younger and older adults. And the idea is to test different doses, of course, but even different constructs, right? So I think the idea is to come up with the best possible outcome and then move seamlessly into Phase II, where you have, I think, 3 plus 1 in older adults and younger adults, so 3 different doses. And so here, sometime, I guess, early next year, we'll have results of that. And again, that will inform how to move into the Phase III.

And do you intend to test it versus the higher-dose vaccines or -- like what's your [ share ] of thoughts?

So there is a comparator, right, in this Phase II study. So this will be a benchmark, for this is flu, so it must be a licensed vaccine.

Okay.

Pierre, what would you say about the mRNA technology overall compared to the current Sanofi products and the number of other assets out there? I mean the idea is that mRNA could address a new strain faster down the road. But I don't know if we've seen that so far yet with some of the mRNA data in flu, the larger-scale data, but it seems like that concept, still, is applicable.

Yes. I fundamentally believe that in flu and other indications, mRNA is here to stick. And if you look at the improvement of the release data from several years ago to now, I mean, it's a major step forward. That's only starting, right? So I think that hopefully with the data we showed in Phase I, we can replicate that in this Phase II, III or I, II, III. And if we do have indeed that low-dose activation in a big sample of folks, but also that reactogenicity, which is proving to be today on the good side, right, I mean I think it's a very exciting proposal because, as you know, right, you can make it faster than the ancestral technologies, right, the protein-based technology. So you have more antigens potentially, and you'll be closer to circulating strains. So your efficacy would technically be better, right? And so if you hit that, but at the same time, you make sure that your vaccine is acceptable in terms of tolerability, then I think you really have something differentiated.

Yes. It feels like it's the next -- it's the first step with mRNA technology and -- relative to standards of care and flu, but there's a lot more optimization. But I think the ceiling on it seems like it's pretty high.

I mean exactly. And so how fast do we get there to be -- we don't know yet. But it's a sense of history, really. I mean, the improvement has been exponential, and I don't expect it to stop right now.

Right. So I don't think you guys have an RSV program that some of your competitors have talked about that. Is there sort of a strategic idea that flu, COVID combo, maybe the -- more likely, going forward? Or is there, down the road, maybe an idea for that?

We don't have an RSV program today in the mRNA. We have all the IP needed for RSV mRNA vaccine, right? So nothing hinders us from going there. I think you're right. The idea is -- I think the promise of the mRNA at least is combination, right? So the question is, how many can you combine? And what's your threshold in terms of [ recto]? So this is the game in which you have to play. Maybe getting for 3 at once is probably a lot today. We have to see where we stand later this year, I think, for us. But generally speaking, if you have really that, across the board, low-dose activity, then you could really string up these antigens, right? And then you have really pretty bold vaccine.

Yes. No, I agree. I mean I think that you're seeing the upper limit of adding -- doing dose finding for COVID and for flu for other mRNA companies and then throwing them together, I mean you can't give 800 mil. I mean, it's too much, right? So -- but you guys having meaningfully lower doses allows you to kind of scale?

Well, it's -- yes, that's the path, right? I think everybody is thinking of that. And I'm sure [ other mRNA ] players are doing the same, is how can we get -- expand that window of opportunity by having lower dose efficacy, right, and probably a higher ceiling in terms of higher dosage before the [ recto ] kicks in, right? I think that's really the name of the game. Because in terms of commercial adoption, what drives the vaccine is really the side effect profile, right?

So let's -- along that same line, when you look at oncology, right, I mean, that's always been a market where you've had multiple mechanisms in play, polypharmacy, whatever you want to call it. And mRNA is particularly suited for that. So talk a little bit about your -- how you view CureVac's approach versus other approaches in oncology? The PCV data made a lot of headway. But if you look previously, though, like I don't think Moderna's OX40 data previously was that good. So I guess you have to pick your indication, right, and your antigen.

Well, very true. I mean there's a lot of work to be done. I think there's so much -- there's such a wealth of information that we have today that we didn't have before, right, in terms of understanding of the relevance advantage. And can you address the bulk of the immunogenicity in the cancer setting? I think that's what everybody is working on, right? So we acquired a company called Frame Therapeutics last year, which is a Dutch company, which was specializing and using the latest technologies in terms of sequencing, right, so you go a 100x deep and you sequence the whole genome of the tumor, right? And so you -- instead of looking by the small window and going at point mutation, which are 1% or 2% of the immunogenicity, and the rest of the protein is actually [ correct ], if you look at completely new proteins, there is stemming from chromosomal rearrangement. So here, you really try to attack both [ immunogenicity ] for the patient, right? So -- and you can actually -- when you do that work, you can do in 1 mRNA and [ stick to it ], maybe 2, right? You can do a completely personalized cancer vaccine. So that's -- I mean taking a step back, mRNA is completely [ risk ], and here the [ rectal ] ceiling is less of an issue, right? Because with cancer patients, you can actually go a bit more into that undesirable effects, right, if efficacy is there, right? So I think there is certainly [ lags ] in the technology there, right? The question is how to get the right antigens to the right patients, et cetera, et cetera. But we also have -- in terms of production, we have the big productions for the large-scale things like vaccine, but then you have to have a small-scale production, right? And so we have a printer that we actually codeveloped with Tesla where you actually could make the vaccine for one person, right? So you need to have the whole scale of things. And so -- I mean, the future is very exciting. Of course, it's going to be -- it's not a short road, right? It's a long and winding road, for sure. But there is a lot of hope. And I think the competitor's data is opening a lot of hope. I mean, I don't think we've seen any vaccine providing such a boost to a checkpoint before. So it's the start of long road, for sure, but it's very exciting.

Yes. Charlie, if you want to ask them on the GBM, but before we do that, I wanted to ask you on manufacturing. So just remind us like where you guys are with your capacity? Again, if you look at the mRNA landscape from other companies, I mean, they've invested massively in manufacturing to account for COVID, but you guys -- it doesn't take a lot to get there. So maybe talk about, is that a strategic priority for CureVac? Do you want to get to a certain level of capacity in a couple of years' time?