Thank you, everyone. I'm Andrew Fein, one of the biotechnology analysts at H.C. Wainwright. It's my pleasure to have Alector be the next company this morning. Here from the company is both its CFO, Marc Grasso, as well as Peter Heutink, Chief Scientific Officer. Very nice having you both here. So, you know, maybe the first thing to do is just, you know, take a minute and just introduce the company to people that have less familiarity, and then we'll get into a bit more of the science-focused questions that come up quite often. Great. Great. So even before introducing the company actually, I think, we live in quite exciting times. At this moment, there is the first disease-modifying therapy that, that is on the market, and that, for me, shows the potential of where we can go. I think if we look at, families, caretakers, patients, I mean, this is actually the first time that there is hope that we can actually really do something. So for me, that is very exciting. At the same time, we have to be very realistic also. If you look at the clinical effect size right now, it's extremely modest, and it's very clear that much more needs to be done. And now I come to Alector- of course, why we are here. So I think that these neurodegenerative diseases are very complex, and they're not caused by a single protein or a single process. It's really a much more complex and more like a system disorder. So we think that approaching that from a slightly different way, in a sense, by harnessing the brain's innate immune system, you can actually target a number of the processes at the same time, and that is where Alector comes from. So we search our targets using genetics because we think that's a very strong indicator of what could be a good target and an important target, and we combine that with immunology and neurology. So basically, trying to really change the way that the main cells that function as the immune cells of the brain, the microglia, how they can tackle basically the different processes that are there. So right now, we have two molecules, basically, in clinical trials, late-stage molecules. We have latozinemab and AL101 that are in clinical trials. Latozinemab for FTD granulin, and so granulin is really a receptor for a protein called progranulin that is mutated in these patients, and it blocks its degradation, increasing its level. And the other program that we have is a program, TREM2, which is an important risk factor for genetic risk factor for Alzheimer's disease, and it activates this receptor. And what activation of this receptor does is it really start to really work on all the brain insults that are there and try to remove them. So these are two very exciting programs. In addition to that, I think we have a very strong preclinical portfolio, and we keep investing in that. And we have a number of, I think, exciting targets that we work on, and we hope to be able to tell more about that in the near future. And in addition to that, we also have been working on how to deliver our drugs to the brain. And so we've developed our own brain carrier program or BBB shuttle, however you wanna call it, that in a way will help us when we develop new molecules, whether these are antibodies, proteins, or enzymes, to really deliver them in a better way to the brain, have a deeper penetration, and basically this would hopefully improve efficacy. That's, that's one, but it would also reduce the cost. So that is where we are, and so we are excited about the programs that we have in the clinic right now, but we're also actually extremely excited on the programs that are coming up. I mean, the importance of the field has obviously led to a number of different companies applying a number of different approaches in their efforts to develop next-generation drugs. And a few of the targets, including ones you're working on, are being worked on by a number of different companies. So it might be helpful for folks if you speak about, you know, how your approach is towards targeting granulin, for instance, is different than those of some of the small molecule programs targeting Granulin. And maybe you can also speak about the broad interest in neuroinflammation, and why it's an important aspect as we think about the entirety of next-generation drugs in the space. So our progranulin franchise, let's call it like that. So we have two molecules, latozinemab, that is basically tested really on FTD granulin. So these are people that have a loss-of-function mutation in genes, so they have basically only half the activity. So the goal is really to restore that. And the way we try to restore that is by targeting a receptor for progranulin that really is involved in the degradation of it. And by blocking that receptor with the monoclonal antibody, basically, we increase the level of progranulin, so it can does its function, that is basically helping the microglia to function, helping the lysosomes to function, and basically respond to insults. If you look in the field, I think in a way there are two possible ways of regulating progranulin. One is what we do, and basically, reducing its degradation. The other way would be to basically stimulate expression or do a protein replacement. So I think all approaches have their merit. I think in our case, I think we are the most advanced program, and so we are in a phase 3, so we're looking forward to those data. And I'm curious how these other programs will do. And you wanted to hear more about neuroinflammation? Please. Okay. So I think neuroinflammation is an important aspect of all neurodegenerative diseases. I think the most clear-cut example is Alzheimer's disease. If you look at all the genetic risk factors that have been identified, and there are over 70, the vast majority of those factors really are involved in, in a functioning in the innate immune system. And, so for Alzheimer's disease, it's very clear cut. Immunity, inflammation is really a major driver of, of disease genetically. And you see that, of course, also in patients, where if you look in the brain, there is brain inflammation, especially later in disease. But there is also, in a way, inflammation can be two things: It can be protective and can be damaging. And we think that if you basically stimulate the microglia, and in a way, the immune system, relatively early in the disease, you can actually have very beneficial effects of microglia and tackle the brain insults that are there. Maybe that's a good segue into biomarker data. You know, and in INFRONT-2, you know, you showed biomarker data. I guess, maybe you can speak about that, and then speak about it in the context of the regulatory environment, and you know, how you sense things could shape up going forward. So, as Peter's mentioning, latozinemab is currently in a phase 3 study that's fully enrolled, and we recently received breakthrough designation from the FDA, which is encouraging. That was based on a review of the phase 2 data, and that phase 2 data has a number of components. One of them is matched historical control data, looking at disease progression from a clinical standpoint, using a modified CDR, some of the boxes for FTD. And there's also biomarker components as well, and there's encouraging data there, including, you know, what appears to be a stabilization of NfL, which in other studies, Alzheimer's studies, not clear how important a marker that is in the context of these neurodegenerative diseases from a treatment perspective. But we also saw a reduction in glial fibrillary acidic protein, GFAP, and that's a marker of astrocytosis and inflammation and an important indicator of progression in these frontotemporal dementia patients. And we'll be looking at these biomarkers and others in the phase three. But I would underscore that our approach, and this is supported with recent interactions with the FDA, is to go for a full approval on the basis of the phase three. And we can talk a little bit about the powering and the assumptions from a clinical standpoint. Is an opportunity always to have, I think, you know, a flexible approach, if you know, from a clinical standpoint, the disease progression is not what we hope it to be. However, I can tell you that, you know, we're well-powered to see a slowing of disease progression down to the mid-20s based on how we're powering. The biomarker piece, and we've seen this with other agents in the area, particularly in a setting like FTD, where there's no approved therapies, you know, could be a path where you could also pursue accelerated approval or approval just based on biomarker changes. But again, our base approach is for full approval. I mean, you brought up the issue of powering, and I guess that question comes up pretty often. You've changed the number of patients, right, INFRONT-3? S o we recently, you know, it was actually not that recent, mid last year, you know, met with the FDA and went through an exercise to, based on the observations we've seen in the longitudinal cohorts in the field, so all FTD and GENFI follow patients, and also based on a blinded sample size reestimation of our own study, can look and basically see that the variability, particularly within the symptomatic patients, is predictable, and it allowed us to focus the primary analysis on the symptomatic patients. Now, the study is also enrolling pre-symptomatic patients, but focusing on the symptomatic patients where the progression is, you know, predictable with less variability, allows us to have an adequately powered study. And we had set a range of 90-100 symptomatic patients to be adequately powered for the slowing of disease progression down, as I mentioned, to the, you know, mid-20s% over the treatment period of 96 weeks. We're well-powered for that. We ended enrolling 103 symptomatic patients, so ahead of that target. And I should also note that's not significantly different than the number of symptomatic patients that we were initially targeting when we started the study. It was gonna be around, you know, 120 or so. When you looked at the split between the symptomatic and the pre-symptomatics, we're basically, you know, in that similar range. That's helpful. You know, maybe we can, you know, switch and speak a little bit about TREM2. You know, obviously, it's another target that has garnered interest from a number of companies now. So maybe you can speak about, you know, the decision to pursue TREM2 initially, as you guys have been for a long time, you know, how your approach is different from the Abeta approaches, that thing. So I think, for me, being a geneticist, so I'm slightly biased in this. No, but I think the genetic evidence of TREM2 as a genetic risk factor for Alzheimer's disease is really compelling, and it really increases the risk for Alzheimer's disease at least threefold. And it's also a risk factor for FTD and other diseases, but the risk for Alzheimer's disease is compelling. And I think the strength of looking for TREM2 as a target is that the genetics really fits with the biology. So TREM2 is really a receptor on microglial signaling receptor, and it senses insults to the brain. And it's a very wide range of insults that it can respond to. So it can respond to apoptotic cells, to damaged neurons or myelin debris, but it can also respond, for example, to misfolded proteins, and these are amyloid or bad amyloid, but they're basically all amyloid. So it could be tau, it could be synuclein. It's, it's very, very wide. And so that for us, made it very attractive. And I think what it basically, the antibody that we developed activates the receptor, so basically makes makes it very susceptible to the signal. So it can still bind to all its ligands, so it's not just activated and goes randomly after everything that it finds in the brain, but it really gets still activated by specific targets, such as amyloid or myelin or whatever, and really then sets in motion a cascade of events to activate the microglia to take care of that insult. And so the antibody activates, but it keeps it very specific. And so, as you mentioned, there are a number of other companies that work on this as a target. I think Alector is the most advanced in this program. We're now in a phase 2 that is fully enrolled, and we get the data readout by the end of the year, so we're very excited. And I think other companies do either antibody approaches or small molecule approaches. The antibody approaches are somewhat similar, but they might bind to different places in the receptor and have a slightly different effect. The small molecule is an interesting approach. In a way, it's a complicated approach because you need to cluster. So as we say, the receptor center is difficult with a small molecule. It's actually easier with an antibody. But if it works, it would be amazing. So we're looking at this with interest, and I think the data there are much earlier, so I think they're in the mid of phase I. But we're looking forward to those results as well. Does the importance of TREM2 as a target, I guess your confidence in that, has it shifted at all over time, I guess, as the AD immunotherapy landscape has changed? I would say actually on the contrary. But I would say that right now. But, no, I think, actually not so much. We think that because the way we approach it, so we're activating microglia and allow it to basically respond to a number of insults. And we know that in Alzheimer's disease, amyloid, of course, is the first pathology that comes up, but then we have tau pathology, we have myelin damage, we have a lot of other things. And we think that, basically TREM2 would be able to approach all of these insults, so not just amyloid, but also tau and other insults. So we think it could work very well as a standalone, still. But we also think that, it could work in a combination or in a sequential approach. And so I think there is, there remains value, and given that the landscape is, of course, that maybe some of the current therapies become more common, it would be a very good, for example, follow-up, but we do think that it would be excellent as a standalone as well. In regards to the Phase II data, do you have a sense of... You know, there are lots of different ways to define success. So as you think about, you know, designing the next program, you know, what would you like to see from the Phase II results that would most inform, you know, your ability to design the next program? So the phase II, it's designed, as a, you know, biomarker-rich, imaging-rich study with, also the clinical and functional measurements as, an important, you know, primary endpoint. The totality of the data is really gonna be important in what we're looking at. So what we'd like to see is, a slowing of disease progression. Now, whether that, you know, meets statistical significance or not, I think is, you know, that's a question, and we can talk about the powering here. But what we wanna see is a slowing of disease progression associated with some important biomarker changes. And as Peter was alluding to, given the broader mechanism of action of, the microglia in this context, we, you know, it'd be great to see that we're, you know, that's demonstrated with the biomarkers. So, you know, it's w e can talk a little bit about the ARIA or what appears to be ARIA that we've seen in this study, which you know others and we you know can hypothesize may be related to the removal of amyloid plaque. Well, let's see what the changes are in amyloid in this study. But then let's also look at other markers of disease progression, including tau. Given the broader activity of microglia, you know we could see some benefits there. We'd like to also see you know the bigger picture in terms of you know the broader role of the microglia, whether that's you know maintaining and nourishing the neuron and neuronal connections, whether that's astrocytic function, oligodendrocyte function... So this broader picture is something that we'd like to see in the totality of the data. So ideally, slowing of disease progression supported by, you know, biomarker activity. And I think that, and as you know, this is a program that's part of an option deal with AbbVie, is something, you know, that we're interested in looking at, that they'll be interested in looking at as well when they think about their opt-in decision and potential next steps for development. That's very helpful. Maybe in the last couple of minutes, you can speak about the BBB program. You know, it's not an aspect that I don't think you get much credit for as a company. And other companies have spoken about their technology quite a lot. So it might be an interesting area to maybe perhaps we'll hear more about your program, you know, going forward. So it's relatively new at Alector. It's something that we developed, matured basically at the beginning of last year, and we will actually have a webinar in June, going more into detail of that. As a system, it was primarily developed to deliver our antibodies, and in a way, it's a variation on what is available already, so it's at either transferrin or CD98. Because we started later, in a way, we had the benefit of rethinking how others did it and trying to think about what would be a better way of doing it. And we think that it's very important to adapt your brain shuttle to your target, and your target really has a big influence of how it delivers, what are the kinetics, et cetera. So what we've done is basically really built a very flexible toolbox of all molecules, which means that molecules with a higher affinity, a lower affinity, which has differences for delivering different time of arms of the molecules, whether there's an active effector arm or non-active. So we have built all these, and then we have built both a transferrin system and a CD98 system. And again, these are very different kinetics. So transferrin can be very fast, and CD98 has a slower uptake but lasts longer. And so there's really differences in that. And what we do is really— So we use it for antibodies, but because we now have the system, we also built into our portfolio programs that look at protein replacement or enzyme replacement, so that was an added effect. But it's really the flexibility that we've built in that distinguishes us from what is basically used by other companies. And in a way, it's like, it's an advantage to be late because you know basically what are the difficulties, and you can basically say, "Okay, we can circumvent these." Very helpful. Great. Well, I think we're out of time, but it was a very helpful talk. Very good talk. Thank you very much. All right. Okay.