Great. Good afternoon, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler, and before I begin, I'm required to point out certain disclosures regarding the relationship between Piper and our next presenting company, CureVac, which are posted at the back of the room and also at the registration desk. So we've all heard a lot about mRNA over the last few years, but not as many of you have heard of CureVac, and I believe this is something that's really going to change going into the new year. CureVac partnered its infectious disease vaccine development with GSK, and is also developing cancer vaccines in its own right. Additionally, CureVac partnered with CRISPR Therapeutics to develop next-gen editing approaches, and there's really a lot that this technology can do, so I think we're just scratching the surface. Here with us from CureVac today is CEO Alexander, and also CFO Pierre Kemula. Thank you both for being with us. Thank you. So maybe for those of us who are not as familiar with CureVac, please start off by describing the company's history just a little bit and the pioneering work you've done in mRNA. Sure. So, I think we are a real pioneer in this space. The company has more than 20 years experience in mRNA. mRNA is all we do, so we're fully focused on this, and we have really deep expertise when it comes down to technology. It's something we understand really well, and this is paired with a really broad patent portfolio. And I would say we are one of the few companies that can really do mRNA end-to-end, you know, from research, technology, to development and producing it as well. So that's CureVac in a nutshell. We have around 1,000 people listed on the stock exchange, on the Nasdaq since 2020, right? And we are headquartered in Germany with a few offices, you know, in different places as well. Yep. Excellent. Well, that's really helpful. So let's jump right into your proprietary cancer vaccines. Moderna and Merck recently reinvigorated interest in the cancer vaccine field with positive phase 2 melanoma data. Maybe just to kind of start and set the stage, what are cancer vaccines? How do they work to educate the immune system against tumors? The principle is the same as you would use with Covid or with flu, right? So we design mRNA in such a way that it forces the body to express certain antigens, right, that are relevant for cancer. Those are then presented on the surface of cells and hopefully stimulate the immune system to attack, to attack those, all right? Our approach is on two fronts. One is we have so-called shared antigens or off-the-shelf vaccines, all right? And the other one is personalized cancer, cancer vaccines. Shared antigen or off-the-shelf vaccines are vaccines that are suitable for certain tumor types or indications based on an overlap of shared antigens between different patients, right? So they're off the shelf and therefore easier to, to produce. In our case, we have the first of that vaccines are already in the clinic. It's for glioblastoma, it's an aggressive form of brain cancer, but where we use eight known antigens of relevance for glioblastoma, pack them on an mRNA, and then hopefully can stimulate the immune system to fight off or hold back the tumor, right? I think the next generation will be where we use antigens, not just that are based on the literature as we have for CV for GBM now, but really based on our proprietary antigen research that we strengthened last year by the acquisition of Frame Cancer Therapeutics, right? And, you know what? You can see what Moderna, BioNTech, and others are doing. You see more and more use cases for off-the-shelf shared antigen vaccines. On one hand, for kind of hot tumors where you have the immune system present already in combination with checkpoint inhibitors, we hope, we believe we can potentiate, you know, the collaboration with checkpoint inhibitors. We've just shown some preclinical data as well, that you, with cancer models that are resistant to checkpoint, you know, therapy, we, we believe we can break that resistance to checkpoint, to checkpoint therapy. This makes some of these so-called cold tumors hot or more suitable for immune therapy. We see more use cases as well. For example, we've shown that we can extend the persistency of T-cell based therapies in combination with mRNA vaccines, so CAR Ts or others, right? So we see more and more use cases on the shared vaccine space. That's one element of our focus, where we're working on. The other one, a bit more transformative, potentially also a bit more behind, is then fully personalized cancer vaccines, where we basically, based on full sequencing of the genome and based on some proprietary algorithms, then really do fully personalized cancer vaccines. Perfect. You mentioned your lead cancer vaccine, CVGBM, which is in a phase one glioblastoma study. Tell us about... First, let's start with the indication itself. Why go after GBM? It's maybe a tough hill to climb for a first cancer vaccine. Maybe I'm wrong about that, but I think a lot of people have that opinion. So why go after GBM first? Yeah. It's not your classical IO indication. I think you're right there, but, you know, there's a high unmet need, right? So far, you know, immune therapies have not worked well in GBM, and that's part of the reason why we chose it. We just started a phase 1 trial, which is currently in dose escalation, where we use the same backbone or so-called second generation mRNA backbone that we use in our flu and COVID programs, as well, and then we pack them with antigens, you know, that are relevant for CVGBM, based on the literature and based on previous clinical experience. We are currently in dose escalation at the third dose. Right. What we're trying to learn from this trial is, it's the first trial in oncology with our second generation backbone. So we look at whether we can elicit the immune response to the antigens that are part of the vaccine, so CD4 and CD8, you know, T cells. So that's the main purpose of the study. So it's kind of a proof of concept in oncology. We are already working on kind of the next generation of vaccines, as I mentioned, where we used our proprietary antigen discovery engine. And there we go more into classical, let's say, IO indications, such as, you know, we're looking at lung cancer, skin, head and neck, so more maybe the indications that you would expect. So additionally, on the GBM, before we get to some of the other approaches, and I'd love to talk about the Frame acquisition too, because I think it's a really powerful approach. What would next steps be? So if you see that you're eliciting immune response as measured by CD4/CD8 T cells, would you then go into a randomized study? What would you see as sort of the go, no-go decision for CVGBM? What do you see as next steps? Yeah. So I think we primarily use it as a proof of concept for the platform that would inform not just what we do next in GBM, but also what we do next in general with the shared vaccines. So I think that's one thing. So this particular study is in patients that were resected for the tumor, so they're tumor-free, right? So in terms of seeing responses, you know, it takes a bit of time, you know, because you would see... need to see whether you can prolong remission. So we will look at that, but the primary purpose of that study is more to inform us, you know, can we elicit the immune response we want? Is it safe, right? So that's the primary purpose of the study. And then it depends a bit on what we see, right? We're in dose escalation, then we go to dose expansion, then we will decide, you know, what we see. There's a high unmet need for sure, right? But, you know, but we will pursue the other programs in parallel as well. So let's get into that. So you mentioned the acquisition of Frame. How do they... You know, there's a sea of antigens out there, right? And, I don't know why I'm making a fishing analogy, but you're sitting there trying to fish for the ideal antigens. How does Frame help you do that? Yeah. So I think the key about designing good vaccines is picking the right antigens, right? So that was the rationale between the Frame Cancer Therapeutics acquisition, because there is a deep knowledge, not just on the biology, but there's a lot of artificial intelligence and algorithms that come in to make sense of all the data that we generate. And our approach is slightly different to what some of the other companies are doing. Whereas some other companies are just sequencing the exome or the coding part of the genome, we really do full genome sequencing, right? And we're looking not just at known antigens, we're looking at splice variants, we're looking at frames and frame shifts. We have already discovered some not published or really proprietary antigens that we believe could be really, really important. So we took a really comprehensive approach of really analyzing the full genome, right? And that's the technology we brought in-house or accelerated, I would say, through the acquisition of Frame. Do you envision where this will be a shared antigen for a given cancer type, or would these be shared antigens really across a broad range of cancers? How do you kind of prioritize? Yeah. So the way we look at this, we basically look at how many patients share the same antigen with the same tumor types. That's what it basically means. And we do a whole analysis looking at hundreds of tumor types and see what is the overlaps between antigens, between different patients. And based on this, we decide, okay, which cancer type is suitable for a shared antigen approach, right? And we have a list, you know, kind of prioritized list of about 10 of those, right? And then based on this, you know, we kind of tailor the approach versus, okay, what is an approach suitable for an off-the-shelf shared antigen vaccine, and what approach or what tumor types would be most suitable for a personalized approach, right? So it's really data-driven based on an analysis of in-house, but they're very big public databases as well out, and we really crunch billions of data sets, right? Yeah. To really get there. Yeah, it's a really cool approach. Can you give us a sense beyond GBM, what are some of the interesting areas you may pursue, interesting cancers that are kind of percolating up to the top? Yeah. Yeah, I mean, nothing unexpected, at least for the shared antigens, right? These are the more, I would say, classical IO cancers. You know, you could look at lung cancer, you could look at head and neck, you could look at some forms of colorectal cancers as well. You could look at skin, right? Here, it's more a strategic decision then as well, you know, looking at what some of the competitors are doing. Then you still have to decide on where do you target. Do you go more into the early stages of the disease? Do you go more in late stages to combine? You combine with what, right? So there's a lot of, you know, decisions that go into where exactly you want to play, even after you've chosen the cancer type. And then the other one, I just said, you know, that we see more and more use cases, you know, combining it with different approaches than just checkpoint inhibitors, CAR T or T cell-based approaches, right? So we're looking at- Yeah ... see where, you know, can we have all these use cases and then, you know, who to do it with. Yeah, makes a lot of sense. To that point, you guys selected GSK for infectious disease. Would you envision doing one large partnership for oncology, where you maybe partner all of your cancer resources with one group? Or do you think it would be more kind of product by product or indication by indication basis? How does that make sense? Yeah, ideally, I, you know, I think probably one larger would make more sense rather than a lot of smaller ones, right? So that would be our preferred approach. Larger also in the sense of, you know, ideally, you would have a partner that has a broad portfolio that would make sense to combine with, not just checkpoint inhibitors- Yeah. But maybe also beyond this, right? So there's a portfolio play, and then obviously, you know, I see the sweet spot for CureVac is not doing large, expensive clinical trials, phase 2 and 3, right? Our sweet spot is in, is in kind of innovation and doing some of the early work, and then beyond, it would also be too expensive, and from a risk profile, wouldn't make sense. So it would make a lot of sense for us to partner then. Yep, makes a lot of sense. As we transition into your infectious disease portfolio, remind us the terms of the GSK alliance and why it made sense to partner these vaccines with GSK. Yeah. Maybe, Pierre, do you want to outline that? Thank you very much. So we have two main collaborations with GSK. So we have a broad infectious disease collaboration agreement, which was pre-COVID or, yeah, signed before we did the COVID agreement. So it has five targets, right? One is made public, which is flu, right? They invested, at the time, EUR 150 million in equity in the company. They own 7% of the company, and they, we had EUR 120 million up front, right? And then all along these targets, you have the development milestones, the regular milestones, the commercial milestones, and then you have your classic royalty, you know, revenues coming from that. This collaboration is very different from the COVID, which is a 50/50, for which we have, basically, you know, a cap at $100 million, which we have reached, right? So the idea is we didn't want to be running into the wall with too much money. So now all the money will be paid for by GSK as we go forward, right? So in these collaborations, we have territories where we would sell the products, which is Germany, which is an important country. Yep. As it sets the price, mostly in Europe, right? And then Switzerland and Austria. So these are the main, the main And then we have a collaboration on COVID and flu combination, which would sit somewhere in between these two. Nice. Awesome. So you guys completed the enrollment of the phase 2 study for mRNA COVID vaccine. Firstly, how do your mono and bivalent COVID vaccines differ from some of the other mRNA vaccines out there from Moderna and Pfizer-BioNTech? And then when could we get data from this phase 2 study? Yeah, I mean, what we see so far with our second generation backbone is low dose activity, meaning we've seen in our phase one trials for both COVID and flu, that we can elicit very solid immune responses at extremely low doses, and potentially lower doses than what the competitors have shown with their own backbones. Meaning you could have a similar efficacy with potentially less side effects, right? And, and then, you know, if you take it a step further, when the end game, I think for many of the mRNA vaccines, could be actually combinations of vaccines, right? And there, you know, if you have to... And, and we know dose is responsible for some of the adverse events that you've seen. So if you combine different vaccines and you can do it at a lower combined dose level, that could be an advantage. Yeah, absolutely. Right. So that's true for both COVID and for flu, right? The COVID, as you mentioned, right, is fully recruited. It's roughly 430-patient study, where we compare against the licensed mRNA vaccine, right? So it's gonna be interesting, not just because it's COVID and what we see from a phase two in COVID, but it's by some way, it's gonna be also kind of a head-to-head against, you know, a platform from a competitor, and we will see what our platform can do and whether it's differentiated or not, right? The study has a bivalent, you know, construct, as well as a monovalent construct compared against the bivalent construct from an approved competitor, right? So and that will inform then, of course, this strategy to go into phase three. We expect the data early next year, right? So that's what we're looking at for COVID. Great. Excellent. So describe your seasonal flu vaccine candidate, and maybe you can walk us through the phase 1 data that led you to candidate selection. Yeah. So the phase 1, we are now in phase 2 of a combined phase 1/2. The phase 1 was very broad. We had 12 different arms, where we looked at different candidates in terms of valencies, right? We have up to eight different antigens that we packed on an mRNA. We had different dose levels, obviously, because what we wanted to do, we wanted to have a vaccine that offers broad coverage, right? Including all the known A and B strains, right? And therefore, we did quite an extensive phase 1 trial, which then informed, you know, which candidate that we take into phase 2, which we then did, and the phase 2 study has started recruitment and is ongoing. Have you characterized that candidate? Yeah, we've characterized a dose. I mean, you know, often the question is, you know, where do you see the value proposition of mRNA-based vaccines in flu versus some of the established, vaccines? And, you know, what we see is, I think there's definitely... And you have A and B strains, which are the main strains. If you look at efficacy of the classical vaccines in the flu space, you know, it's kind of mixed. Usually, it's between 40%-60%, depending on the year and how well you match the strain, right? So we do believe there's room for improvement on A strains in terms of efficacy. Now, B strains, even though they're less relevant, usually from a clinical point of view, because a large part of the morbidity is driven by the A, by the A strains, and a lot of the disease burden, let's say, and pandemics and epidemics is driven by A strains. Nevertheless, we need to bring coverage for the B strains as well, and B strains historically has been a bit harder- Yeah. Not just for the classical vaccines, but also for the mRNA vaccines. Therefore, you know, we did this broad phase one study where we also used non-equimolar designs, meaning we had different proportions for that code, for A versus B strains, you know, different weightings, if you want to see how we can get the broadest coverage. Plus, we did some more antigen engineering as well to see whether we can tweak it even further to have really a competitive program in phase two. So I think there's still room to differentiate, showing superiority on A strains and at least non-inferiority, well, I would say on B strains. That would be quite a good target product profile. And then, as I said, I think the end game will be more... I think COVID and flu lend itself quite nicely for a combination because both of them are yearly vaccines. You know, the risk profile is similar in terms of patients, patients that need it, right? So I, I think that could be a really differentiating piece then, versus the non-mRNA vaccines. So just to ask, maybe in a little different way, is this a quadrivalent vaccine? And have you described how the molarity is set up between the A and B strains, or is that not yet disclosed? It's not disclosed. Okay. It's definitely the multivalent- Yeah. Maybe, maybe quadrivalent, maybe more. Yeah, multi. That means more than one. Definitely. Got it. Definitely. Well, that's... I just want to make sure I get it. In our phase 1, we had up to eight different antigens. Yeah. Yeah, really cool. I mean, it's one of the great strengths about mRNA, and I think ultimately it's going to lead mRNA to actually be superior to traditional versions. Yeah, it's much more versatile, right? You can really play around with it much more easily, right? Yeah. We really, last year, we created more than 1,000 different constructs, right? That's the beauty of the technology, right. Cool. Now, just touching on this briefly, but I also know that you're working on a rabies vaccine, CV7202. What is the latest development plans there? Are there other infectious, disease vaccines like this that you're working on with the Gates Foundation? No. Rabies was one of the earlier programs that preceded me, right? We use this as kind of a proof of concept- Yeah ... trial, right? But the point is, in our view, we don't use just mRNA to do the same as you can do with other technology, right? Yeah. We try to use it in settings where you can really use the technology to an advantage and produce a better product, right? So that's why we use this as kind of a proof of concept, but we're not going to pursue it further. Tell me how important mRNA manufacturing is, especially when it comes to negotiating partnerships. You guys have this RNA Printer. Tell us about that. It's pretty cool. Yeah. So mRNA manufacturing is hard, right? There are a lot of companies that say they can manufacture, but when you go into detail, it's usually not so easy, right? So it's hard. It's kind of like cell therapies in many ways, right? So it's hard. And for partnering, it's really, really important, right? Because it would be really hard to find partners to partner with you if you cannot manufacture mRNA. So for partnering, it's absolutely key, at least to support some of the initial clinical trials, right? These kind of early trials. So it's really, really key that you can have this kind of end-to-end, at least for the clinical manufacturing, you know, manufacturing as well. Otherwise, you know, you rely on our external partners, you're not in control of timelines, so you have issues with transferring your technology and so on and so forth. So it's a real benefit. Yeah. Yeah. Especially the scale to commercial. Yeah. That's important. The printer, you know, the printer to your, you know, the printer, we have a large factory, right, for millions of doses that we're completing for flu and COVID, but that wouldn't be suitable for smaller batch sizes. Right ... or for personalized approaches, right? So the printer is a modular approach, highly automated. It really, you know, it's about as big as, you know, half of this room, right? So it's really versatile and would be really, really suitable for small batch production or for pre-production of personalized cancer vaccines. We just got the first milestone this summer with the first manufacturing license for an mRNA cancer construct. And the idea is to really have this end-to-end optimized system and then kind of a framework manufacturing license that you can produce, you know, different kinds of cancer vaccines on it. Makes a lot of sense. So I usually don't ask too, too much about patent cases, because I figure I leave that to the lawyers and then read the press releases. But is there any update on the ongoing patent suit with BioNTech? I think there was recently maybe a ruling or an update that happened. Yeah. So there are two cases ongoing in two territories. One is Germany and one is the US. The US has a trial date set for October 1st, 2024, right? There are 10 different patents at play, so that's, you know, set up and we'll know more late 2024. In Germany, we have eight different patent rights at play. Germany is a bit complicated because they have kind of a bifurcated process where validity and infringement is determined by different courts, right? So each patent right is determined validity and infringement and then kind of come together. The important milestones will be towards the end of this year, where one of our first patent, GC enrichment patent, which is important because it covers a large part of the early phases of the pandemic as well, right? And there, we will get a final ruling at the end of December, right? Okay. And then the other ones, you know, will play out, sometimes in 2024. Great. Well, we'll keep an eye out for that. And then, Pierre, if I may ask you a last question. I think you guys ended the third quarter, very healthy cash position, EUR 464 million. If I do my math right, that's over $500 million. How long does this fund the company? What's it enabled CureVac to accomplish? Yeah. So yeah, I agree with you. We have no debt, but we have a clean balance sheet, and this cash position will allow us to go till, you know, mid of 2025, right? So we have an important horizon ahead of us. But importantly, we are also working currently on identifying a way to try and extend that runway by, you know, being more selective on what we do in our organization as well, right? So- Okay ... well, that's a bit in the making. It's not fully finished yet, but we hope to be able to provide more clarity on that and extend that runway a bit more, you know, looking forward. Great. Obviously, any new partnerships, which is bring in more- Of course ... more cash to- Yes, sir extend that runway and enable you to do more. Work on that as well. Great. All right. Well, thank you so much for being with us. Thank you. All right. I really appreciate it. Thank you. Thanks very much.