Today, two of the Jefferies London Healthcare Conference. My name is Lucy Coddington. I'm one of the European Pharma and Biotech Analysts based here in London. It's my absolute pleasure to introduce Andrea Pfeifer, the CEO of AC Immune. We're going to kick off with a short presentation, and then we'll move on to questions. If anyone in the audience has any questions, please raise your hand, and we can get the mic to you.
Thank you. Thank you, and welcome to my presentation, which will be focused today on some of the recent development, but also I want everybody to give a very short introduction to the company. I do not think it is forward.
That's good.
Oh, okay. I just have to okay. This is a disclaimer. All right. In summary, our very focused pipeline has several phase two products and also has multiple wholly owned assets. The key differentiation of AC Immune is the precision medicine approach we are taking in neurodegenerative diseases and our leadership in active immunotherapy. Our pipeline is built on the two platforms, the super antigen technology for the active immunotherapy and our Morphomer platform, so small molecules. These platforms and the molecules have been validated both by clinical development as well as by BD. From our partnerships, we have generated more than $430 million, and there is potential for additional more than $4 billion in these partnership milestones as well as royalties. We have cash until Q3 2027, which allows us to reach important key inflection points as well as to accelerate our investment into our precision medicine approach.
This is our pipeline. As you can see here, it has three phase two programs in active immunotherapy and also a phase three program in diagnostics. The lead programs in active immunotherapy, so the ACI-35.030 plus the ACI-24, are partnered with Johnson & Johnson and with Takeda and have both fast-track designation by the FDA. Our wholly owned asset, the ACI-7104, which is an active immunotherapy against alpha-synuclein, is in phase two development and will release additional data by the end of this year concerning pharmacodynamics as well as clinical readouts. As I already said, we are also investing in complementary small molecule programs targeting intracellular pathological alpha-synuclein and also the NLRP3 pathway.
Today, I will mainly focus on our innovative programs, so the small molecule programs for intracellular targeting, which we believe is very important for the overall disease progression which we see in neurodegenerative diseases. Before I go to the individual programs, I would just like to get your attention on precision medicine and why we believe that precision medicine, precision prevention is so important in neurodegenerative diseases. Just taking the examples of Alzheimer, there are about 100 million Alzheimer patients today with prodromal Alzheimer or Alzheimer dementia, but there are about 300 million people with the risk to get Alzheimer, which in fact is the global prevention market we are looking at.
As you can see on the right, our active immunotherapies and small molecules have the ability to address the complexity we see in neurodegenerative diseases driven by different proteins, a beta, tau, alpha-synuclein, and also TDP-43 as much as the inflammasome. It is really the combination of active immunotherapy and the intracellular targeting, which we think is important for the prevention of neurodegenerative diseases at the earliest stage of the process. Now moving to our intracellular targeting. The intracellular targeting is achieved with small molecules. It's really small molecules derived from our platform, from our Morphomer platform. What these small molecules can do, they actually get readily into the brain. They can also enter compartments, cellular compartments, very nicely. They bind conformation specifically and also selectively to misfolded proteins.
Because they can be orally applied, they are cost-effective and convenient for a patient, meaning that we really expect that such molecules will be readily available across many pathological and disease stages. This shows you now what we see in tau. The small molecules, which I will show you in a second, can actually really inhibit the intracellular aggregation, which is on the left. They can actually inhibit also the spreading by addressing the external aggregation. Both together, the intracellular and the extracellular process inhibition lead to, in fact, the protection against neurotoxicity in tau, which I will show you now in a few experiments. These are really data which are very important.
You see on the left that our Tau morphomer, which is called 664, can inhibit in 4510 mice, which is a very aggressive Tau model and builds both soluble as well as insoluble Tau, as well as shows neurotoxicity, and that you can see here. In fact, these morphomers reduce the Tau pathology, the Tau burden by more than 50%. You see in the middle that it also addresses soluble high molecular Tau, which is essential for neurotoxicity, as we have learned now. On the right, you see, in fact, that the molecule can reduce neuronal loss, so really neurotoxicity when applied in this model. Taken together, this means that these Tau small molecules have a potential to have a preventive effect on the AD pathology, and we expect them to be broadly applicable for the different stages of the disease.
Now let me move to the NLRP3. Again, using our Morphomer small molecule platform, we also generated molecules against the NLRP3 pathway, as you can see here on the left. This is where our molecules actually inhibit the NLRP3 pathway. We have today two small molecule categories: ones which go into the CNS, and here we are in IND/CTA stage, and the other ones, so the peripheral acting small molecules which are in the lead stage. These NLRP3 inhibitors are broadly applicable in the CNS applications, such as Parkinson's, Alzheimer's, multiple sclerosis, as well as in peripheral disease, in particular the metabolic diseases and inflammatory diseases as much as neuropathic pain. This is the summary of our NLRP3 lead, the CNS lead 19764, which actually has a very competitive profile, as you can see here. It enters very readily into the brain.
It has a high potency in multiple in vivo and in vitro assays, as I will show in a second, and it has an excellent safety going up to doses of 400 milligrams per kilogram. I will now go into more details to the experiments which you see here marked in red. You see on the left that a single dose of this NLRP3 inhibitor causes a very nice brain penetration, very competitive to the best-in-class molecules in the field, which is very comparable to the CSF and, in fact, the plasma. In the middle, you see in this whole human whole blood assay that the molecule, our CNS molecule, generates a very nice effect on the interleukin-1 beta release, a marker of inflammasome activation. This is done in concentrations, in IC50 concentration in the 20 nanomolar area. Last but not least, this is an in vivo model.
It's a multiple sclerosis model. One more time, you can see that our inhibitor really reaches the targets and reduces the activation which you see in the EAE model. I just show two more results here. This is, in fact, the activation of the inflammasome in an AD-relevant model. Here, chronic application of LPS leads to both the inflammation, no inflammation, as well as to effects on cognitive learnings and cognitive performance, very similar to what you see in an Alzheimer patient. As you can see here on these three different graphs, LPS leads, in fact, to an increase in neuroinflammation of the microglia as well as the astrocytes, as well as also to NFL enhances in CSF, which is linked to neurotoxicity.
When you inhibit with daily, twice per day, 30 mg per kg, this activation, you see that you achieve significant decreases, in fact, more than 40% for the microglia, 80% even for the astrocyte activation. Also, the CSF NFL, which is a very important marker for neurotoxicity, is positively influenced, saying that altogether the inhibition of the NLRP3 pathway by these molecules has a very high potential with a disease-modifying effect in AD pathology. Last but not least, I would just like to show you that we also were very interested in the DIO model for obvious reasons, in particular since the results of a competitive molecule in phase two were published showing a very important decrease of inflammation in humans.
What you can see here is that even in the DIO model, you have this very high reduction of the microglial inflammatory response, as much as in the astrocyte inflammation. Again, bringing together the consistency of high inhibition and high specificity around this NLRP3 pathway by our lead molecule. This brings me to the milestones. As we announced in our Q3 earnings, we have not changed any of the milestones expectations. On the ABATE trial in phase two, partnered with Takeda, we will agree on the communication with Takeda. However, following the 12-month data release, which is happening in December, we hope to be able to communicate on the 81, 82, and 83 cohort.
Importantly, on the 7104, so our wholly owned active immunotherapy against alpha-synuclein, we still expect, after extensive communication this year, results on immunogenicity, on biomarkers, and in particular also on pharmacodynamic results as much as on clinical outcome. As I mentioned before, we're taking several of our small molecules, very important for the intracellular targeting, into clinical lead or lead candidates. We will start, in fact, the IND CTA submission by December, starting the clinical trial by the beginning of next year. Last but not least, both of our tracers, the alpha-synuclein tracer and the TDP-43 tracer, are in clinical development, and we will have data on this also by the end of the year.
With that, I say thank you, and I would just like to remind you of our overarching goal, which is to move the treatment paradigm of neurodegenerative diseases to a precision prevention and, in fact, early treatment of a disease before, in fact, the disease arises. Thank you. Okay. Thank you, Andrea. Thank you for the presentation. Let's start with 7104 then. That's one of the upcoming catalysts before the end of the year. You mentioned we're expecting some data. Perhaps you could talk us more through what that data exactly is and what the implications are for the rest of the program. Yeah. I mean, it's a very important data point because we will have 12 months' data of the total cohort of 34 patients. It is relatively important that we had seen excellent immunogenicity with about a 20-fold increase over baseline after four injections.
All of the patients showed positive response, and we expect additional immunogenicity data. Safety has been excellent all the way through. What is really important is that we will see the alpha-synuclein reduction in the brain induced by this active immunotherapy. We also hope to report already clinical readouts for this program. We are really looking forward to that because it will be one of the most advanced programs targeting alpha-synuclein in Parkinson's disease. With the reductions in alpha-synuclein that we might see, is there any evidence yet that can link those reductions to clinical outcomes? You might remember that we have published a phase one B study in Lancet Neurology, where we have already seen a correlation between the titers and, in fact, the reduction of the alpha-synuclein in CSF. This reduction in CSF was positively linked to trends in clinical performance.
We hope that we can actually repeat the data or actually see more. Got it. The part two of the trial, then, how will that differ to what you've done so far and build on those findings? Yeah. We are heavily preparing for part two, assuming that the data will be encouraging. It will basically trigger the part two of a clinical study, which is a study with more than 150 patients, which is a study that can give us proof of concept and transition into a phase three development. Is that something that you would like to continue conducting yourself, or is this something you could think about partnering as well? That is, of course, my own opinion, and what the company is able to do.
In fact, we are really putting everything together that we can continue at least the next phase in-house because we think it is a very important program. We will see. We will see what the data look like. Great. Let's move on to Alzheimer's. There has been a lot of progress in the last five years or so in terms of monoclonal antibodies that we now have therapies approved, and then we have clinical trials where they are moving earlier in the treatment paradigm. AC Immune's focus is obviously on an active immunotherapy approach. Perhaps you could talk through how that differs and is complementary to the antibody approaches that are perhaps a little more advanced. Yeah. I mean, obviously, we are very happy that we are also progressing in the antibody treatment. This actually really substantiates the hypothesis that immunotherapy actually works in these neurodegenerative diseases.
However, we believe that many of the characteristics of these antibodies are inhibitory for the large preventive application. The active immunotherapy here, we induce the body's immune system to generate the antibodies to have a continued long-lasting immune response, which is specific for the pathological protein. We believe that the safety is key. In fact, I was just at a conference in Alzheimer, and one of the things reported is that safety is all important for people in a non-symptomatic state to really consider treatment. As you know, we can today diagnose Alzheimer risk 10 to 15 years before. The field definitely moves into active immunotherapy because so far it has been safe. It is specific, and it's available. It's readily available for a broader global prevention approach.
The field is effectively going into this direction, and obviously, we are, to a certain extent, leading the field in this aspect. Okay. And then your anti-ABT vaccine, ACI-24, is in a phase two study. Takeda has an option there. You mentioned we might get 12 months' data for three of the cohorts, potentially around the end of the year next year. If that data, depending on your communication decision, is communicated, what can we expect from that data, and what will be the next steps for that program? I mean, again, we have to look into the data. Obviously, we want to see the 12-month PET data and biofluid data to actually make the right decisions. And we obviously also hope to start now very soon the 84 cohort, which gives us more insight or more patient data for this ACI-24 program. Okay.
You outlined some very interesting mouse model data for your anti-Tau morphomer, your small molecule program, showing it addressing both the intracellular activity and then the extracellular pathology. I guess when it is so effective at targeting both aspects of Tau pathology, you also have an anti-Tau vaccine. How could those two work together, or do you need the vaccine if you have such an effective small molecule? Yeah. It is an excellent question, but I would say first, let me just summarize. We were very surprised, together with our partner, about the efficacy which we see in the different parts of the Tau pathology. Really intracellularly, extracellularly, and then the effect on neurotoxicity was so far not described and is linked to a very particular Tau species, which we have not published yet.
This was, in fact, a very positive outcome, and we are quite excited about this news. However, it is clear that depending on which stage of a pathology, you might want to either do alone or even combination. What is important to say is that these small molecules can be very early. They act actually in the first step of pathology when you interrupt intracellularly via Tau aggregation. Number one, it can be given early, can be given long-term because it is oral, and it can be given in combination. We need to see because for ACI-35, we have very positive data. We have shown excellent reduction of biofluid markers in even a phase 1b/2a study. We are really looking forward now to the data readout of a phase 2b study, which is a potential pivotal study in preclinical Alzheimer's.
We will actually know what Tau inhibition in a preclinical Alzheimer's stage will do. I think we can decide what is the perfect combination. The fact that we have to really be intracellular, intercompartimental effect is quite encouraging. With that, your small molecule Tau is partnered with Eli Lilly. Perhaps you could update us on the status of that collaboration and what the next steps will be for your small molecule Tau program. Yeah. I mean, we will make by the end of this year, so very soon, the decision on the clinical lead molecule. We are starting the IND enabling studies, and I think we will report maybe some other additional news, so. Okay. Let's talk quickly about NLRP3.
It's been getting a lot of interest, particularly its attention on the obesity market, but also you've shown your encouraging brain penetration and the potential there for inflammatory diseases. How do you decide which is the best indication to first develop that for? This is definitely a very important question. We are in the lucky situation that we can wait until certain phase two readouts come. We were very encouraged by the recent phase two data by Ventyx to actually show a substantial unseen effect on cardiovascular inflammation. We are HS CRP. We think that the inflammatory response also in cardiovascular disease is very critical in other metabolic diseases. I mean, we really see an application in AD, and I showed you the very encouraging data we have in AD, which is almost a part which is a bit neglected, I have to say.
Everybody's in obesity, but the anti-inflammatory results which we are seeing are excellent in AD, and we are probably going in two paths. One is in neuroinflammation; the other one is in non-CNS diseases. If you have good molecules, you can make these decisions. Got it. With that, we've run down the clock, so I'd like to thank Andrea for her time and for the audio.