Welcome to the Jefferies Global Healthcare Conference. My name is Lucy Codrington. I'm one of the European pharma and biotech analysts based in London. It's my pleasure to welcome Andrea Pfeifer, the CEO of AC Immune. This is a bit of a hybrid session, so Andrea's going to kick off with a presentation, and then we'll move on to questions. Should anyone in the audience have any questions, please do raise your hand, and we'll get a microphone to you. But in the meantime, I'll hand over to you, Andrea. Thank you, and welcome to everyone. I'm happy to give you an update on AC Immune and all the recent news which we had. Here the disclaimer, and let me just start with a short summary. So we have one of the broadest and de-risk pipelines in the CNS space, with 16 diagnostic and clinical and therapeutic programs. AC Immune today is focused on active immunotherapy, and you will see later on that these are some of our most advanced products. One of our major factor of differentiation is our precision medicine approach in CNS, copied from oncology, meaning we are developing therapeutics and diagnostics together for better patient selection, better clinical endpoints, and so on. We are very successful in partnering of our products. We have recently made another important deal with Takeda, and I will go into the details a bit later. But so far, we have actually generated about $450 million from these deals, and we with a probability to have another $4.5 million of potential milestone payments. Our pipeline really is derived of our two platforms, and you will see that we continuously generate some of the best-in-class products. And last not least, we have now with $105 million cash plus $100 million upfront, we are extremely well financed into 2027 to generate, in fact, the value inflection points, but also develop our active immunotherapies. Now, this is our pipeline. Our pipeline contains seven clinical products, five in therapeutics and two in diagnostics. As you can see from the pipeline, there are three active immunotherapies in phase II development. So with our clinical pipeline, we cover some of the most important targets in CNS, targeting Abeta, Tau, and alpha-synuclein. The clinical pipeline is complemented by our preclinical assets, which target TDP-43, a fourth target in Alzheimer’s disease, alpha-synuclein, and also the inflammatory target, which is NLRP3. Some of our targets are, as I just showed, partnered, but some of them are not, and we very carefully select now the assets which we develop in-house and generate the high value, which is linked to the products which I just showed with Takeda. Now let me switch to our, I would say, most important value-creating part of our company right now. This is active immunotherapy. In contrast, to, monoclonal antibodies, with, active immunotherapies, they actually generate a long-lasting antibody response, via a type of vaccine approach. So, secondly, we can actually, because of this long-lasting effect, which we are generating, think about an annual or biannual application. I think the most important aspect is actually the safety of these products, because we have not seen any ARIA-E in any of our clinical studies. And, connected to this active immunotherapy is, of course, the, logistical and economic benefit of an active immunotherapy, which is very different from a monoclonal antibody. So we have, I will then further highlight, in fact, ACI-24.060, so the product which we just partnered with Takeda, and I will also mention the ACI-35, where we have now entered a potential pivotal study together with Janssen. I would also like to mention that, we have a very strong portfolio around alpha-synuclein, alpha-synuclein being a major target in Parkinson's. And here we have the active immunotherapy in phase II. We have a small molecule, and we have, in fact, the a diagnostic coming with it. Speaking about the ACI-24, so these are the deal terms. So, the agreement is about the ACI-24.060, the active immunotherapy, where Takeda received an exclusive option to license the product, the global rights to ACI-24.060, against the payment of $100 million. In addition, we will receive a low- to mid-hundreds of millions exercise fee, and the exercise is linked to a clinical outcome of our ongoing ABATE study. Together with this exercise fee, the overall payments are about $2.1 billion, and this is separated in the exercise fees, plus regulatory development and commercial milestones. Upon commercialization, we will receive royalties again in the mid- to high-teen% on net sales. What is also important to say is that the progress of the program is supported by an active collaboration in order to ensure that both parties are fully aligned. I might also mention that we are taking care of the preclinical development in case anything is necessary, but we are also funding and conducting the ABATE studies of the cohort 1, 2, and 3. After exercise of the option, Takeda will take over and take care of the funds as well as the conductance of the clinical trial. Takeda is also responsible for the regulatory as well as the commercial activities of this program. Now, this shows you what is behind this product. The vaccine is definitely best in class because it generates antibodies against the 2 most toxic Abeta species, so the oligomeric Abeta, as well as the pyroglu Abeta. The product received a Fast Track designation last year. The reason why this product is so unique, you see here, it's actually a liposomal construct, where the antigen is anchored on the surface and mimics the conformation, the pathological conformation of a targeted protein. So this antigen then drives the antibody response towards antibodies against the pathological Abeta species. We will report later this month the first Abeta PET data, as well as later in H2, the 12 months data of the Abeta PET readout. Now this shows you the study. So, we are well advanced in our dose selection study, and we are now in part two, which is the extension of the ongoing first and second dose, and in fact, the start of the Down syndrome study. As you can see here, the outcome measures are safety, tolerability, immunogenicity, Abeta PET, as well as exploratory biomarkers and clinical endpoints. What is important to say is that the oligomeric response of this vaccine is very specific. It's a factor of 1000 and very similar to lecanemab. We are expecting the 6 months and the 12 months data later this year. It's important to mention that the study will remain blinded, but we will show individual patient-level data of Abeta PET. Obviously, we... If there is a reduction of the plaque of the Abeta plaque, then this would be the first indication about the effect of this ACI-24 vaccine on the Abeta plaques, as well as the timing when we can expect the effect of such an active immunotherapy in comparison to an antibody. Now I'm moving on to the ACI-35. ACI-35 is an anti-tau vaccine. It's partnered with Johnson & Johnson. The product is derived again from the same super antigen technology, so the liposomes, which I showed you before. In a head-to-head comparison, the ACI-35 performed better or best of all the other candidates, and we saw a very specific response, very high response, an unprecedented high response against the pathological Tau, which in fact led to the decision of Johnson & Johnson to bring this product into a phase IIb study, which has a potential registrational activity. So, this is now the study protocol. As you can see here, the ACI-35 is in fact being tested in a preclinical Alzheimer's population, which is very important. So the subjects do not have a disease. They are selected by Tau PET imaging and preselected by P217, so it's a biomarker-based pre-screening process. Because we are looking into a preclinical population, we expect, in fact, to prevent or slow the tau pathology and also to potentially prevent the onset of a disease. The secondary endpoint shown in the middle is a tau PET readout, which we are looking at baseline and every year for four years. The patients are treated over a period of four years at zero to six months, and then every six months. We hope actually, if a tau PET imaging shows an effect, that we can use it for an BLA application and also for an accelerated approval. However, we have a primary endpoint, which is in fact a cognitive endpoint, where we are looking at via PACC5. This is an endpoint, a clinical endpoint, which can identify changes very sensitively in preclinical Alzheimer’s. We hope that this endpoint will allow us to again get a traditional application or a traditional approval based on what we are seeing in this study. The pre-screening of this study works extremely well. We now have many patients already pre-screened. We were very surprised how quickly, in fact, the screening can happen in such a complicated population. These are the expected readouts and the expected milestones. So we see, you can see here that obviously, the year is represented by the readouts in ABATE, so the anti-Abeta tau-PET imaging results. You can see here that we have 6 months data as well as 12 months data. We also will have a first patient in the ReTain study, so the anti-Tau vaccine study, together with Johnson & Johnson, and we will have the first immunogenicity data and in fact safety data for our Phase II alpha-synuclein active immunotherapy in the second half of this year. We also have multiple preclinical assets coming through. For example, the TDP-43 antibody, which will complete the preclinical development in the first half, being ready then to go into the IND enabling studies. And we will have other preclinical assets, such as small molecules against alpha-synuclein, TDP-43, as well as NLRP3. So there is a large preclinical pipeline behind the, of course, value drivers, such as the active immunotherapy. And this is just summarized here. So while the main value is behind the clinical pipeline, which I just showed you, but I want to remind you that we have wholly owned assets, such as the alpha-synuclein active immunotherapy, which I just mentioned is in phase II, the small molecule for alpha-synuclein, the TDP-43 antibody, which is in IND-enabling studies, as well as I would like to mention the NLRP3 assets, so antibodies and small molecules. NLRP3 is an extremely important asset in inflammation, and we are hoping to take this in CNS diseases, and the probability also to work together with other companies on obesity and non-CNS diseases. I'm almost at the end, so I think in summary, we can say that, really, what we are standing for is scientific excellence. Each of our products had the opportunity to make excellent partnerships. The recent deal with Takeda has supported our leadership in active immunotherapy, and we want to obviously enhance this leadership. Besides now the clinical aspects, we have these preclinical assets, which we want to further develop with the money we have now available in our company. And last, I would like to remind you that the overarching objective of AC Immune is really to change the treatment paradigm of neurodegenerative diseases towards prevention. I'm of a firm opinion that the best we can do for our patients is actually to prevent the disease rather than to treat. Thank you very much. Thank you for that introduction, Andrea. And before I kick off with my questions, just to check, is there any questions from the audience to begin with? Nope, we'll move on. Okay. So, you talked about the upcoming PET reduction data for your ACI-24. What have you seen preclinically in terms of Abeta plaque reduction that might guide us to what we might see in the six- and 12-month data? And then are there any factors we should consider when comparing an active immunotherapy approach to an antibody approach? Yeah. Well, obviously, we are pioneers in active immunotherapy, so some of the questions you're asking, we don't have yet the answers. But, what I can say is that, the ACI-24 has really this unique profile of, having a polyclonal response specific for the, most toxic Abeta species, so the pyroglu and the oligomeric Abeta. And, based on our non-human primate data, the titers which we are seeing with specificity of response, would, I would say, indicate that we should see a very, positive effect on the Abeta PET. Now, the key question is: when do we see this? And here, this is really what we are sort of, I wouldn't say struggling with, but that's what we are really, looking at with, a certain, yeah, expectation. Obviously, we are not speaking about monoclonal antibodies, but we're speaking about an active immunotherapy where you have to build the titers in the body, meaning it probably might take a bit longer to achieve the same antibody titers, as you will see with a monoclonal antibody. So, we would expect that the optimal response will be probably around the 12 months data. On the other hand, having said this, comparing a polyclonal response against the most toxic compounds with a monoclonal, which targets only one, could actually also lead to a synergistic effect. So, short-term or, and long-term, we might end up with a more efficient drug. But really, the most important aspect for me is that we have not seen any safety signal. So when we are speaking about Alzheimer's, we're speaking about prevention, this is where the field is going, and the only way from my perspective that you can really prevent the disease is with a drug which does not induce severe side effects, can be given in a very simple way, potentially once per year or twice per year, and is economically valuable. So this is why I think we need to really compare these two things, and that is, for me, a very clear indication that active immunotherapy is the way forward. Great. You mentioned the lack of ARIA-E to date. Why is it that you think you can have good plaque clearance and still manage to avoid ARIA-E? Well, nobody knows. But what our assumption is that because you avoid these spikes, which you have with a monoclonal antibody, which obviously is a short, very strong exposure in the body, but you really build this antibody titers over time, you avoid – if you avoid the spikes and if that, you avoid the side effects. And I think there are quite some data now coming out which speak in this direction. But what is also important is, in fact, the long-lasting effect. It's not just that you have these injections every 2 weeks, as you need, for example, lecanemab, but you might really get away with 6 months or 12 months, and that's for the patient and the families, such an important benefit that I would believe it will really support the launch of such a product. Then, I guess, you've had this deal with Takeda, which is impressive in terms of deal terms, but what dictated the timing of that deal, considering you are so close to this initial six-month data? I guess competition. It was a very competitive deal, but at the same time, from our perspective, we wanted to give this drug the optimal development possibility in terms of timing, in terms of financial means. I mean, the development of such a product for prodromal and preclinical Alzheimer's. We're speaking about $hundreds of millions, maybe $billions. And if the data are already very promising after six months, then we need to be ready to invest. And if you then start to make the deal, we might get slightly better deal terms, but we might lose a year or more, and I did not want to take this risk. So we really, the timing, the partner, yeah, the reflection on what we can do as a smaller company and what we can do with an excellent partner like Takeda was a very... Made the decision very easy then now. Okay. Moving on to one of your other partner programs, ACI-35. You mentioned about this potential for accelerated approval based on the tau biomarker data. I guess, is there enough understanding and science behind tau in the way that we know there is about A beta to justify an accelerated approval? Yeah, that's a very, very good question. And it's a complicated question. I mean, obviously, from the monoclonal antibody data which we have, everybody accepts now more or less that the Abeta PET is a surrogate marker for clinical outcome. In tau, we are not yet there. I think we will be, like we did before, have to pioneer some of it, by, in fact, validating the tau PET as an endpoint for tau therapy. So we will do some of this work. We are running also parallel studies, again, to further support tau PET as such an endpoint. But, we believe if the right data, obviously, we combine this also with biofluid markers, et cetera, et cetera, and many interim analyses, that we can actually convince the FDA that this is a, an approach, at least where is on a different target, a, a similar path forward. And if we have good data, I think it's always about data, we certainly have some of the best imaging, specialists in Johnson & Johnson. I think we should be able, to achieve that. Great. You mentioned now your cash runway is extended into 2027, and you did a quick run-through of your unpartnered programs, but which of those are gonna be your priority, assuming Takeda does opt in to ACI-24? The first priority is absolutely our alpha-synuclein active immunotherapy for Parkinson's disease. It's very well advanced. We expect the first data. If the data are positive, which is in H2 this year, then we will carefully think about starting a potentially pivotal study, and we will do that in-house. So this is definitely where our money will be going. NLRP3 is a very important target now in inflammation. We seem to have one of the best brain-penetrant compounds, so obviously, this is a target in many CNS diseases and recently now also in obesity. So this is something we probably will also develop in-house. Then we will decide on the other aspects depending on the priorities or deal possibilities. Okay. We've run down the clock perfectly with that. So I'd like to take this opportunity to thank Andrea and also the audience for your attendance.