us for today's fireside chat, with CureVac. I'm Evan Wang, one of the biopharma team senior analysts, and I'm pleased to be joined by Alexander, CureVac's CEO. Let me turn it over to Alex for a quick intro, and then we'll jump into Q&A. Yeah, thanks a lot. Thanks for the opportunity to be here. Yes, I'm the CEO of CureVac. Started almost a year ago, April last year. Still very excited to be here. CureVac, as many of you know, is a real pioneer, fully dedicated on mRNA. You know, really unique capabilities in terms of doing end-to-end mRNA, from research all the way to small and large-scale manufacturing, very strong patent portfolio, making great progress on the pipeline, and really trying to build, you know, a clinical stage, a stronger clinical stage company. Great. So, you know, you've been at CureVac for, you know, just over a year. As you're looking, you know, at positioning in 2024 and longer term, I guess, at this point, how do you see CureVac, and how are you kind of positioning for, you know, a winning strategy longer term? Yeah. So we have kind of... It depends on what you look at. We have kind of three focus areas that we're working on. Obviously, infectious diseases, prophylactic vaccines, collaboration with GSK, where it's 2024, it's a very important year for us as we have the readout of two phase II trials, one with COVID and one for flu, which obviously would lead then, you know, to late-stage development programs and additional, you know, combination therapy studies in the field. So sure, we're gonna talk more about it. That's one thing. The second pillar that we're quite excited about is oncology. I worked in oncology the last 20 years, and I do believe that, you know, mRNA-based vaccines, it's ripe now for oncology, based on the progress that we're making on the antigen discovery side, based on progress we're making with our own backbone and on the delivery and some of the data that we're seeing in the space. So, you know, we have a phase I trial ongoing in glioblastoma, which is a first proof of concept trial, and we see data shortly, so we're excited about that, that as well. And we're looking at some use cases beyond infectious disease and oncology, where we believe mRNA technology is uniquely positioned to really, you know, bring a benefit and a therapeutic approach. So we're making progress on that as well. So all in all, 2024, it's gonna be a really, really important year for us. Great. Just starting with infectious disease, you know, had some phase II data from COVID. You know, we'll have flu coming out, but, you know, I think important here is, you know, I guess you're partnering with Glaxo, really one of the leaders in vaccines. You know, we've all seen Arexvy. Can you just recap the partnership structure, you know, where we stand, and I guess GSK's expertise as a vaccine partner in some of its development choices? Yeah, maybe I start with the with, you know, GSK as a partner. Obviously, GSK is a key player in the vaccine field, very strongly positioned, and from that point of view, a great partner for us. We have two different collaboration agreements, one for flu, which is a bit more straightforward, a licensing agreement, where, you know, they run all the phase II and III programs and beyond. The COVID one is slightly different. It's a 50/50, you know, co-development profit share deal with investment for us, capped at $100 million R&D costs, which we achieved, right? So those are the two programs. They have additional slots they can take as well in terms of additional targets. So overall, you know, very good partnership for us. Very happy with the progress that we're making. Great. You know, and you've really been focused on the second-gen backbone across your mRNA programs, and specifically, you know, we've seen some of the data there in COVID, in flu. You know, I think GSK has given a pretty strong endorsement there. I think they've talked over GBP 3 billion longer term and peak sales for flu in its combo. So I guess what's been so interesting and differentiated about the second-gen platform, I guess maybe as context relative to some of the approved vacs, mRNA vaccines that we've seen? Yeah. What we've seen with our platform, starting from the phase I, you know, that we've shown last year, and then even the phase II COVID data that we just presented or highlighted just prior to JPM earlier in the year, that is, we are able to elicit very strong immune responses at very low doses, right? So this low-dose efficacy, which we believe is relevant, especially in prophylactic vaccines, for two reasons. One, we know that dose is linked to side effects, right? So the lower you can dose, I think the better it should be in terms of the side effect profile, which is very relevant as we are treating healthy people, you know, to a large extent. That's one thing. And the second thing I think that is gonna be important, maybe more in the mid to long term, is we believe the... What's very interesting is gonna be combinations, especially combination of COVID and flu, right? And we believe mRNA as a platform is uniquely positioned to really do combinations, and in the combination, again, the cumulative dose matters, right? And in addition to that, it's not just the dose, but especially for flu, the valency will matter as well. And in our phase I flu trial, we studied a large number of multivalent constructs that could have the benefit of providing a large coverage, right? So, you know, the ability to do this at a low doses, giving high valencies, you know, positions us very well, and that's why we are quite excited about our platform. Great. You know, just on the COVID data that you shared in January, and I think you're preparing for phase III there. Can you recap, you know, I guess, what we saw there in terms of some of the immunogenicity?... and especially on the safety side, I think a special focus for some of these mRNA vaccines? Yeah. So just to recap what we studied in the phase II, right? We had two constructs. One was a bivalent construct that codified against the BF.4-5 variant and the wild type, and the other one was a monovalent construct against the BA.4-5 variant. And the control arm was COMIRNATY, right? 30 micrograms. So it was interesting for us, not just because it's COVID in the phase II, but we had a direct head-to-head comparison against, you know, an established standard of care. And what we didn't display, you know, the doses that we used for competitive reasons, but even our highest dose was significantly lower than the COMIRNATY 30 microgram dose, right? So, and what we've seen is, we've seen, I would say immunogenicity or efficacy that is at least, if not better, than what COMIRNATY has shown, and, reactogenicity or side effect profile that is potentially a bit advantageous for us, right? So that's why, you know, we're quite excited about the data we've seen, right? And that's why, you know, we are, you know, preparing for phase III. We're still having discussions with health authorities, how that exactly is going to look like. It's a bit more clear in Europe, versus the U.S., but that's what we are currently working on. Great. Then, you know, with flu, you know, you're conducting a you know, a very robust phase II study, over 1,000 patients, you know, with your multivalent approach. I guess, how have you and Glaxo approached influenza? I know we've seen some challenges here, and some successes, but I guess, you know, what are you looking for when you design this program? Yeah. So as you said, very robust study, 960 patients, two cohorts, one for the younger adults, 18-64, and then the other one, you know, 65+. Both of them compare against the relative standard of care, right? So it's going to be a very robust data set. And of course, we're going to look both at immunogenicity and reactogenicity. The phase II is fully recruited, and we expect data relatively shortly, right? So we will see that data set relatively shortly. And the phase II is a result of a phase I, and in a phase I, we looked at a lot of different constructs with different valencies, right? To do two things. One is, you know, of course, you look at A and B strains. We do believe there's still room for improvement versus traditional vaccines on the efficacy side, especially for the A strains. And on the B strains, right, it's trying to figure out what the right approach is to, you know, to B strains, and we've seen based on what Moderna and BioNTech have done, you know, it might need some tweaking, and we've did some tweaking as well to optimize, you know, the, the approach for B strains, because, of course, we need to be at least, as good as conventional vaccine on B strain and potentially superior on, on A strains, right? So that's kind of what we're working on. Great. And I guess, you know, as you're thinking about older and younger adult populations, I guess, how do you define success in each, especially with an mRNA vaccine? And if you could comment on it from both maybe immunogenicity and safety. Yeah, I mean, you know, we will compare against the standard of care, right? It's going to be a very robust data set, so you will have a direct comparator, and hopefully, you know, of course, we want to be able to differentiate against, you know, currently established vaccines. So we will see, and we know what we want to see internally in terms of, you know, potentially improving efficacy. So we will see, we will see that relatively shortly, but, you know, we believe just the ability of the mRNA platform to produce closer to the virus, simpler manufacturing, it's going to be cheaper as well. So we believe mid- to long-term, mRNA has a lot of potential and future in this space. And then I think the end game will be combinations, where I believe an mRNA platform is uniquely positioned versus the more classical platform, which is much harder. And for me, especially, combos with COVID and flu, right, make a lot of sense. Both are yearly vaccines. The risk patient population is very similar. The timing is the same, right? So, you know, we're looking forward, of course, to look at both individual vaccines and then start working on the combination. Great. You know, I think we've seen development approach from Pfizer and Moderna focused on different populations. I guess, does it make sense to look at both younger adults and older adults for combo and flu with mRNA? I guess, how are you guys thinking about that? We will see a little bit, right? We need to see... You know, once we see the outcome of the phase IIs, then we have the phase II COVID. We know the data. We will see flu relatively timely, and there we look at the different cohorts. So then we will need to see whether it makes sense to have kind of a one-vaccine-for-all approach or whether we need to tweak it. But that's why, you know, we have a very robust phase II program, which will allow us then to make the right decision for phase III and moving forward. Great. Then, you know, last thing on vaccines. I know the Glaxo partnership includes, you know, other targets, and I believe opt-in decision is this year. I guess from a strategic perspective, you know, if Glaxo, you know, chooses not to elect on some of these targets, are you guys interested in maybe developing some of these as a standalone? Probably not as standalone, but we do have some areas, and not just for viruses, but we're looking at potentially also, you know, bacteria, including resistant bacteria. We're looking at other approaches as well, where there could be a few targets that could be interesting, but most likely we would do that as well in collaboration with other companies. Great. And then I guess beyond the respiratory targets, you just mentioned some material targets. I think we're seeing some emerging data there.... I guess, what's your excitement there? Yeah, I think we will need to really look closely, right? We do want, we do wanna go into targets where we believe mRNA technology brings an advantage versus other conventional technologies. So we will need to really see very carefully where we play. But we do see some unmet need potentially in some pathogens, you know, that we could uniquely address with mRNA, right? That's what we're looking at. Great. And then, you know, turning to oncology, you know, I guess for those unfamiliar, you have a pretty extensive background in oncology, where you're global head of oncology at Sanofi and also led Avastin at Roche Genentech. So, you know, I know cancer vaccines has been a pretty emerging space over the last year from a competitor program. Can you talk about the focus on oncology and the opportunity with mRNA? Yeah, I'm quite, you know, obviously, oncology has been riddled with failures when you look at vaccines. Right? Now, why do I believe that is changing, and why do I believe mRNA could play an important role? I think we have kind of three things coming together that makes me much more convinced that we really have something in our hands that could work in oncology. One is ability to pick the right antigens, right? With any vaccines, it stands and falls with picking the right antigens. And we do have now the tools. For example, in our case, we do full genome sequencing, looking at really the, we have a much better understanding on tumor biology. We look at short and long-acting RNAs, as well, and all of that we bring together, and we use a lot of bioinformatics to try to pick the right antigens, and the field has made huge progress over the last three to five years, and we cannot do things that we were not able to do five or 10 years ago. We have a good backbone, we know, the backbone works well for oncology as well. Plus, you know, big, progress as well on the delivery side, which helped to fail back just five or 10 years ago. We just couldn't get the mRNA into where we wanted it to go. All of that together, plus, you know, some of the data that we're seeing, you know, from other companies and from some of, of the academic institutions, you know, make me quite confident that, you know, we have a way forward. And of course, the big advantage of mRNA is you can iterate very, very quickly, right? So we can see what's happening, we iterate. For example, last year alone, we produced more than 1,000 constructs, you know, to really see which one works, which one is the best one. So I think we're still early, but I'm really excited about the potential in oncology as well. We see also more and more use cases. In our view, you know, we have off-the-shelf vaccine. We're working on personalized cancer vaccines as well. We also see more use cases, for example, in T-cell-based therapies, where, you know, the issue you have, whether it's CAR Ts and others, they kind of exhaust over time. But what we see is, you know, periodic boosts with the vaccine, you know, they come back up. Right, so all of that, seeing more use cases and just based on the data that we're seeing internally and externally, I think, make me quite excited about that space. Great. I guess from an indication perspective, you know, are there areas where cancer vaccines may be more applicable? Yeah, we look at- More exploratory? We look at two different things, right? On one hand, we believe there's still a room for kind of shared antigen or off-the-shelf vaccines, because, you know, we did a lot of work on mapping and kind of seeing where overlap of antigens could be between different indications and different patients, and we definitely see some indications where that makes sense. I think these are probably more the classical, let's say, IO-based indications, whether it's head and neck, lung, skin, and maybe others, where we believe an off-the-shelf approach could make sense. Right? So that's one piece, and the other one is, of course, more personalized cancer vaccines, which could include a broad variety of cancers. The second question then linked to your question is then, you know, at what part of the kind of, you know, patient history you go in with the vaccines? Probably makes a lot of sense early on in the disease, where you still have an immune system that is more intact, where you still have a tumor microenvironment that is still more or less hostile, you know, I would say. And then, of course, the later you go into the disease, you will have to do combos, right? And it will depend a bit, as you know, cancer is not one thing. Mm-hmm. Very specific approach is based on the indication. But I think we will learn a lot over the next, you know, few years on where to play exactly. And then on the personalized things, which could be potentially transformative, I think the manufacturing piece is gonna be really, really important as well. And also there, we're quite well positioned. We have a printer, which is kind of a, you know, modular device, kind of almost like this room, a bit smaller, right, that is fast, that is highly automated, and that will allow us to do the manufacturing piece as well. Great. And then, you know, I know it's still pretty early innings, and we're seeing a few different technologies, even with mRNA out there, and approaches, you know, I guess whether it's conventional versus self-amplifying, you know, different backbones, different algorithms, different delivery devices. I guess, how have you been doing your work into developing an optimized version, you know, with the backbone, with, you know, the antigen section, all, all, all those that you mentioned before? Yeah, of course. I mean, we're looking at all of this. I think there are a few things where we definitely still wanna further grow. One is on the whole antigen discovery piece, right? Because that's gonna be a really evolving field, so we're very actively looking at new ways or additional ways of doing that. Two, just, you know, trying to improve the linear backbone where we currently play. There's still some tweaks that our scientists do on a daily basis, whether it's caps, whether it's different tails. The delivery side, I think we still have a lot of room to improve, because if you look at the LNPs, for example, that are currently used, they're not very customized, let's say, for the use, because we use mostly the same LNPs, whether it's for oncology versus infectious disease. But the field is doing a lot to have more, I would say, targeted approaches when it comes to delivery, even cell-targeted. So I think that's gonna be still a lot. Of course, we are constantly looking at other mRNA-based approaches, whether it's self-amplifying, whether it's circular. We have our hands on a lot of these, right? I would say so far, we haven't seen something, at least in our hands, that is really superior to what we are doing. But of course, you know, we don't want to be out-innovated in our own field, so it's something that we are currently looking at and see what is kind of cutting edge, what is coming, and make sure we're a part of that. Great. And you've partnered externally or acquired externally with some of the antigen discovery, you know, work. Can you just talk about some of the acquisitions and kind of developments you've made on that space? Yeah. We, we bought a company about 18 months ago or so called Frame Cancer Therapeutics, which of course, is kind of a boutique company, really heavily involved in antigen discovery, which is a combination between really understanding the biology, but then applying a lot of bioinformatics as well in that space, and we integrated the company, so that brought a lot of capabilities in-house. We also partner with a company called myNEO, also in the antigen discovery space, and we continue to partner, partner with them. So that's definitely a space that we're going to continue to look at, whether it's collaboration, whether it's strengthening our own capabilities, for sure. Great. And then, you know, in the clinic, you have a proof-of-concept study in GBM. Can you just- Yeah, we have a proof of concept study with GBM. It's a phase I trial. I would say that's kind of the first generation, I call it, shared cancer vaccine. First generation in the sense of that here we took antigens that are known to be of relevance in glioblastoma and packed them eight, you know, in this case, and packed them into a second-generation platform, right? And what we're looking for... The study has recruited really, really well, which is not easy in oncology because it's very competitive. We escalated already to the maximum dose of 100 micrograms. So what we're looking at primarily in that study are biomarkers, i.e., to see whether we can elicit CD4, CD8 T- cell responses against the antigens, looking at cytokines. Secondary is then looking at more clinical endpoints. So we're gonna learn a lot from that study to help us already with what I call kind of the second generation off-the-shelf vaccines. And those, you know, we already have clinical candidates. We hope to start it to the clinic in 2025, and these include then antigens from our own proprietary discovery work that we have done, some known, but also some novel ones. Great. Can you give us a, I guess, maybe a glimpse into, I guess, how you're thinking about the next gen candidates? And I guess, is it the antigen... You mentioned the antigen kind of work there. I guess, how does it look, I guess, maybe from an immunogenicity profile, or are you kind of looking to kind of further increase the immunogenicity profile or just? Yeah, definitely. Right. We are looking at, you know, very specific... Those are-- the off-the-shelf ones will be indication based, right? So we are-- we have done extensive mapping, you know, on, on antigen discovery, so I think we know what we want to see. I think the whole field is still trying to figure out, you know, it's a numbers game to some extent as well, you know, where you need-- how many antigens do you need, you know, versus picking the right ones. So that's something that we are still looking at, but that's the beauty of the platform because we can iterate very, very quickly, right, to see. So that's something that we're looking, we're looking at. But, you know, at the end, we want to get to the clinic as quickly as possible because you can only learn so much. But once you're in the clinic, we can learn, we can learn a lot. There's still a question around, you know, are you gonna use modified versus non-modified in oncology? There might be some benefits of using non-modified in oncology versus in prophylactic vaccines, you maybe don't want to stimulate the innate immune system too much because you don't want to create too many side effects because you're treating healthy people. Whereas in oncology, you probably want a strong activation of the innate immune system, right? So the jury is still a bit out there, you know, what we're gonna do, and we're looking at both, right? So, you know, we're looking at all of this. We wanna have a really data-driven, science-driven approach. Great. That's with the shared antigen side. I guess, when can we see maybe the first four and the personal cancer vaccine side? Yeah. So we're doing a lot on the research side. We're doing a lot of testing of different constructs, right? With different numbers of antigens as well. We're doing a lot of work on LNPs. We're doing a lot of work understanding how, you know, we need to play, looking at the whole value chain, including manufacturing, because that will be really, really key to have this end-to-end approach in personalized cancer vaccine, because time will matter, right? So we're looking at that. It's still gonna take us a bit of time to bring it to the clinic because also, you know, we need to work very closely with the regulator because, you know, every product, every vaccine is its own product, right? But nevertheless, you know, we are looking and fast following into the footsteps what other companies, what other companies are doing. Got it. And just in the context of your oncology franchise, you know, a pretty costly area to develop, I guess, how are you thinking about potential partnerships here? And I guess maybe what, what kind of data would you have to, I guess, you know, just have, I guess, generate the best value for yourselves and- ... Yeah. So, definitely we wanna produce more data in the clinic. That's also I think what partners, what partners are looking for. Definitely, I think we want to partner because oncology, right, we cannot go as fast as we would like to on our own, and it's risky and it's costly, right? So we do have-- we see growing interest, I would say, on the partnering side, based on, you know, some of the data that we are showing and based on some of the data that are out there. So, definitely 2024, hopefully for us, will be a very important year also from a partnering perspective. Great. And just, you know, making sure we have time to talk on IP side, you know, can you remind us, you know, some of the kind of upcoming global proceedings for 2024, you know, that investors should look to maybe put into context, the decision we got in December as if it relates to these at all? Yeah. I think what's important to understand for IP is it's really a long game, and, you know, we believe we have strong IP built over the last 20 years. You know, we believe some of the inventions that some other companies have done, you know, are on the back of our IP, so we feel quite strongly about our IP. There are two jurisdiction, maybe just to clarify. One is the U.S., which is a bit easier. In the U.S., we have a court date on October first. It'll be a few weeks trial. We have 10 different patent rights at play, and in the U.S., it will be one procedure that looks at infringement, validity, and damages, right? All in one, all in one go. So that's a bit easier to understand, starts in October, all right? And then we'll see how it goes. The other jurisdiction is Germany, which is a bit more complicated because in Germany you have kind of a bifurcated process. You have one court looking at infringement, another court looking at validity, and then it comes together. But also there, we had eight different patent rights, and each patent right is like its own trial, if you want, right? And now we will see how they plan out. You mentioned we had a result just before Christmas, which was not in our favor, which we appealed, and we believe we have a strong case. But here we just need a bit of patience to see how it all pans out. That's one thing, and the second thing is, you know, we don't need to win them all, right? If we win one or two, and given the big denominator of sales that we're talking about, it's gonna be more than enough for us, right? We need a bit of patience, see how it pans out. We're quite confident that we will win something, and something is gonna be enough for us. Great. So sounds like a bunch of clinical and non-clinical- It's gonna be an exciting year for us, definitely. Great. Thank you so much. Thank you.