Time to join us today at another session at the Baird Healthcare Conference. For those unfamiliar, my name is Jack Allen, and today I'm joined by the Voyager Therapeutics team. Right now, I have Toby Ferguson, the Chief Medical Officer, and Nathan Jorgensen, the Chief Financial Officer, with me, and Dr. Alfred W. Sandrock Jr., the Chief Executive Officer, who will hopefully be joining us shortly. We did want to kick things off as we have a lot of ground to cover as it relates to the Voyager story. I was joking with the team here. I've got a couple of pages of questions so I could go for hours on Voyager. We do have Al joining us here as well. We wanted to start things off with, I guess, a high-level overview of the company, and then we're going to jump into the recent data on the NeuroShuttle program. Maybe, Toby, if you could just provide investors with a minute or two on Voyager and the story, and then we'll hop into NeuroShuttle. Jack, great to be here. I think broadly, Voyager Therapeutics aspires to be a multimodality neurotherapeutics company. We're historically known as a gene therapy company, but really, we're leveraging that knowledge and the knowledge of neurogenetics to build up a multimodality program. We have a broad effort in Alzheimer's with multiple programs in Alzheimer's. We have a number of partner programs around gene therapy. We've recently shared our emerging data on NeuroShuttle last week. We think that really starts to move the needle towards a company that is broadly focused on delivering things into the brain in a meaningful way. Yeah, you do a great job of queuing it up there. I mean, Voyager Therapeutics has a breadth of technologies and a breadth of ways of attacking neuroscience, and an incredible team of neuroscientists as well working on these difficult issues. I think very well positioned in the broad sense here. Maybe let's kick it off with NeuroShuttle. You did have the data last week on the program. Maybe you provide a high-level overview of that data set to set the stage, and then I have a few questions on NeuroShuttle and how you think about positioning that. Al, thank you so much for taking the time to join us. Thanks for having us. Sorry I'm late. The shuttles come from, they come directly from the TRACER™ AAV capsid discovery platform. We first discover capsids across the blood-brain barrier, and then we say, what are the receptors that they leverage to get across the BBB? Once you've got the receptor, now you can make ligands against the receptor, see if you can conjugate them to various macromolecules, and turn them into shuttle drugs, essentially. That's the way we leverage a transferrin receptor. The first of these is ALPL. For each shuttle, you have to consider three different properties that they may have. One is pharmacokinetics. The data we showed last week showed that ALPL has very drastically different pharmacokinetics from the transferrin receptor. One thing about transferrin receptors is that there's a very high Cmax in the brain, but then by seven days, it's mostly gone. ALPL has a very much more steady increase in the brain, and even at 21 days, it's still there. We can't even calculate the half-life yet. PK, very different. Distribution. PFR shuttles things into multiple organs in the body, so there's a big peripheral sink, which is probably one of the reasons why the PK is short-lived. That could be an advantage for some diseases. It may be a disadvantage for other diseases where you really would like to restrict the drug to get into the CNS. Three is safety. Transferrin receptor programs, as you know, they all have anemia as part of their adverse event profile, and that's because transferrin is involved in iron metabolism, so you get a decrease in reticulocyte count. We have not seen a change in reticulocyte count with the ALPL program so far. Of course, ALPL has its own function having to do with bone mineralization, so we have to keep an eye on that. Safety, PK, distribution are going to be different. Having an array of shuttles, we think for brain disorders, it's going to be very, very helpful for the field. Yeah, I guess in that context, where do you see ALPL playing versus transferrin? I know there are some transferrin programs that are in the clinic already. I'm not aware of any ALPL programs, but please correct me if I'm wrong. I guess what aspects would you like to bring the ALPL program forward? You're right. There are no ALPL programs, at least none that Voyager is working on in the clinic yet. I was just thinking the other day that, for example, for anti-Tau, as opposed to anti-amyloid, where you want to get it into the brain, it binds essentially irreversibly to amyloid plaques, activates microglia. TFR may be perfectly fine. In fact, trontinimab data is hard to argue with. It's fantastic. For anti-Tau, which has no effect or function, we would like it to stay in the extracellular space for long periods of time. For example, for anti-Tau, that might be perfect. ALPL might be the perfect shuttle for that. For many antagonists, you want to maintain 24/7 coverage, and you don't want to have to inject it every other day. That might be one example. I hope Toby agrees with me because he's the Chief Medical Officer. Certainly do. When might we get some more context around the initial targets, I guess? You did announce the ALPL shuttle data, but you haven't really provided too much context around the exact places you're looking to bring the technology. We haven't. The timing is not exactly clear, but one of the things we'd love to do is to name a program or two in research where we're using the ALPL shuttle. We hope to do that in the coming months to six months or so. Awesome. Another thing I wanted to ask you about, just given your rich partnership history as it relates to the capsids, how are you thinking about the NeuroShuttle program? How much of this do you want to keep internally, and how much do you want to partner? I know there have been a number of deals in this space over the recent months. Just even in the last month, Novartis did two shuttle deals. Yeah, with BioNTech. Cyranex, a Chinese company. I think shuttles are hot right now. You look at the trontinimab data where they took essentially gantenerumab, which was a pretty mediocre antibody for amyloid, and transformed it to best in class, both on efficacy and safety. It's hot. I'm open to partnerships. I like the fact that, first of all, we've gotten most of our revenue, most of our money from non-dilutive sources. We did $500 million in deals on the capsid partnership. You can look to us to do something similar with this other platform. Not only do you get cash, but many of these companies have the kinds of scientific expertise that we would love to engage with. For example, we don't have a lot of chemists at Voyager. If you want to conjugate a ligand to a molecule, if you want to do oligonucleotides, you need chemistry. We could hire people or outsource it. It would be much better to work with a powerhouse that has a lot of resources to bring to bear. Got it. You'd be open to partnerships in the near term and the long term, be it now pre-clinical and clinical. I think our track record proves that we are open for business, and I'm open to any kind of structure that makes sense for Voyager shareholders. Awesome. Yeah, that's great to hear. Maybe anything else to cover on the NeuroShuttle program? I know we could talk about it for hours, but any other highlights that you wanted to touch on? No, I think we hit it all. It has massive potential. Investors are interested, and I think it's going to be exciting next year as we release more data on it. Yeah, awesome. Maybe we can shift gears back to Alzheimer's. Al, I know you have an incredible depth of expertise in the Alzheimer's space. Could you just give us a high-level overview of how Voyager is kind of positioning the pipeline in Alzheimer's? You have a number of different modalities and mechanisms that you're looking to pursue here. I guess what boxes have you not checked? How are you thinking about building out the breadth of the pipeline here? I'd say we have two programs against what we think is the next and most important target, which is Tau. I believe Tau is responsible for the neurodegeneration, the actual loss of nerve cells in Alzheimer's disease. It's the spread of Tau that's pathologic. We all get a little bit of Tau misfolding in a part of the temporal lobe called the rhino cortex. That's part of normal aging. When you get amyloid appearing, it triggers the spread of Tau throughout the brain. The stages of Alzheimer's are actually defined by how Tau spreads in the brain. Toby will tell you about the two programs that we have against Tau. Before we do that, I wanted to say that we added a recent new entry, which is APOE. APOE is the most important risk factor for sporadic Alzheimer's disease. Actually, there was a paper in the New England Journal about a year and a half ago. If you're homozygous for APOE-4, you're almost certain to get Alzheimer's disease. You usually get it at a younger age, in your 50s and 60s. You can meet families where APOE-4, over half the family members are affected by Alzheimer's disease. It's a pretty bad disease. I like the idea of preventing Alzheimer's disease. I mean, if you're an APOE-4 homozygote, why wouldn't you want to switch, essentially, E4 to E2? E2 is protective. What we're trying to do is we're trying to decrease E4 and increase E2 and maintain APOE levels constant. We can do that with gene therapy, and we're certainly able to do that in the animals with our program. With that, I'm going to ask Toby to summarize the two top programs. Happy to, Al. We're excited. As Al highlighted, we really think that Tau, for a number of reasons, is the next most important target coming in AD. Its presence and spread in the brain is what correlates with pathologic stages of disease, clinical stages of disease. Our lead program is our Tau antibody program. This is an antibody, pathologic-specific C-terminal Tau antibody. Currently, we're in Alzheimer's patients in a multiple ascending dose study. We're on track for a readout based on biomarkers and particularly Tau-PET in the second half of 2026. It's important to highlight, there's an important external catalyst related to that program. Johnson & Johnson has a large phase II study that's CDR sum of boxes, and Tau-PET are going to be included in that study. That readout is either late this year or early next. We think there's some read-through of that program to ours. We're excited to see those coincidence of two things for the Tau antibody approach. Of course, our other Tau program we're very excited about is our Tau knockdown program. This is our TRACER™ AAV capsid one-time IV-administered gene therapy program. A couple of important distinctions from what I'll call first-generation gene therapies. One, it's an IV-administered capsid that gets across the brain. Two, we shared already some non-human primate data, and we've shared 11-week data in that regard. We think we can get, we've shown in primates, we get substantial knockdown throughout all the appropriate cortical regions at a dose of about 1.3E13 vector genomes per kilogram. That's really important in the context of safety. That's an order of magnitude less than a lot of the current systemically administered programs. A tenfold difference in dose with really effective pharmacokinetics and PD. In addition, we also have the capsids that are designed to substantially detarget the liver. As the group probably knows, liver issues have been a real issue with gene therapy. We have a tenfold less dose, and we thirtyfold detarget the liver. We have some real opportunity there as well. Speaking to the efficacy side, another external catalyst to really highlight is Biogen's BIIB080 data. This is an every three to six-month intrathecally administered ASO, a lumbar puncture in the lower back. That data we think is really important to understand the clinical effect of Tau knockdown. That's coming in mid 2026 as well. That program had shared some earlier data that you can remove pathologic Tau. Compared to baseline, people actually show removal of Tau based on Tau-PET and a potential very large clinical signal. We have two Tau programs. Our gene therapy will be in the clinic next year in patients. We'll have data coming from our antibody program with two very important external catalysts. Yeah, you laid that out very thoughtfully. I guess, what do we know about Tau knockdown and the degree of reduction we need to see? I know there was a UCB data that had some amount of Tau reduction, but maybe it didn't directly correlate with efficacy. What should we be looking for in Johnson & Johnson's data as it relates to Tau knockdown? How are you thinking about if there's a threshold that's necessary as it relates to reductions in Tau at this point? I think UCB, I mean, people certainly view the data as mixed. I think we've viewed it more as glass half full. For the first time ever, an antibody showed in humans, a Tau antibody that you can actually decrease the accumulation of Tau burden based on Tau-PET. Important step forward for the field. Of course, it didn't hit as primary on CDR sum of boxes. It did have an effect on 8S COG-13, an important cognitive endpoint, but not a functional endpoint. I think the unanswered questions there are really, what is the relationship of Tau-PET signal change there to clinical? What we're looking for the Johnson & Johnson data to provide is that understanding in that relationship. We would like the UCB folks to share some of their further thoughts on it, but haven't. I think the Johnson & Johnson data, we've heard it's coming. We're excited to see that data. Is there anything about the Johnson & Johnson antibody that makes you optimistic that they'll see a more robust reduction in Tau? I guess, how do we think about? It's a good question. I think one key difference is that, like our antibody, their antibody is pathologic specific. The UCB antibody binds both wild type and pathologic Tau. If we take a lesson from the beta amyloid field, pathologic specific antibodies was a very important advance for the field. We see that that could be quite important. Jack, I can't resist but say that the reason, you know, you might say, why did we choose our antibody against the C-terminal? It's because we had several antibodies that were pathological Tau specific across the Tau molecule. Of course, nobody wants to target the N-terminal. The two N-terminal antibodies failed in the clinic. Which is the right epitope? Mid-domain, MTBR, C-terminal? Nobody really knows yet. We chose to use this animal model where you have a human transgenic, it's a transgenic mouse that has human Tau expressing in the brain. It's called the P301S mouse. You take paired helical filaments purified from Alzheimer's brains from humans, and you inject it into the brain, and you look at the spread of Tau. What I was saying earlier is that we all accumulate Tau a little bit in the temporal lobe. It's the spread that's pathologic. In this animal, the Tau spreads. We think it might be spreading with the exact same mechanisms that they're spreading in humans. We don't know for sure, but that's what we're hoping. Our antibody blocks that spread the most robustly and consistently. That's why we chose it. The reason why I'm pretty excited about the J&J is that they did a similar experiment and a similar model, and they also show that it blocks the spread. That might have been important in their choosing that antibody too. Now, the cool thing about this model is that it also correctly predicted that the N-terminal directed antibodies would fail, because N-terminal antibodies fail in that model. It had negative predictive value twice. It had positive predictive value. The UCB antibody also blocks the spread. So far, it's three for three in terms of correlating with the clinical outcome. If J&J also correlates, now we would be four for four. I think I would get even more excited about ours as well. We'll have to keep an eye out for that data. The one method with the antibody is to reduce the spread of Tau, and the ASO is to knock down the production of Tau. Yeah, but you know what's cool is what Toby said is that even though you just knocked down the production, you get rid of pre-existing pathological Tau that's in paired helical filaments. We used to think of neurofibrillary tangles where that pathological Tau is, as irreversible. It looks like super aggregated protein. The idea that you can block the production of new Tau and you have removal of pre-existing neurofibrillary tangles, that's what the Bib 80 data seems to show. That's pretty, I never would have predicted that. If that were to repeat, then wow, you know. The antibody blocks the spread. The Bib 80 and our gene therapy decreases production but removes pre-existing Tau from neurofibrillary tangles. How do you see your antibody and your gene therapy playing a role in the clinic together synergistically, or do you see them treating different patient populations given the difference in mechanism? How are you thinking about that development in the long term? I think, Al, we started to lay out this idea that the antibody really is targeted in spread. The knockdown approach, the siRNA approach, really is removing intracellular accumulations of Tau broadly in cells. I think fundamentally, you have this idea that amyloids are needed quite early, and we may get to a point where that's a biomarker-based treatment that comes very early in disease or even preclinically. As you get the emergence of Tau, you could see a place where you want to use a Tau antibody where you've had substantial spread. If you had a fair amount of spread, the antibody is probably not your right modality. I think we haven't commented on it, but the UCB data and others, the Tau antibodies appear very safe. That combination of an IV approach, very safe, early in disease before there's a lot of spread is probably where you put the antibody. The Tau knockdown approach, if you have a patient who's got a fair amount of intracellular Tau already accumulated, broader spread, maybe the knockdown approach comes in. There certainly could be complementary different stages of disease. I think importantly, we've learned, started to learn over time clearly that Tau levels with beta amyloids really affect how effective the treatments are. Earlier with lower Tau, you do much better. Likewise, with Tau-based therapies, we'll learn which patients are responsive and not responsive, and we'll fine-tune it. Fundamentally, you can see a place for each of these therapies across the spectrum of disease. Yeah, how would you elaborate on that and fit in the APOE program? You have a vectorized monoclonal antibody against beta amyloid as well. Where do you see those playing a role in the treatment? APOE is a very interesting question. Fundamentally, I think what I'd said with APOE, Al's already highlighted that people get disease early. The disease is worse. It's quickly progressive. What we haven't said is that none of those patients, or very few of those patients, get amyloid therapies because of the high risk of ARIA, and a higher risk of severe ARIA. There's worse disease, no therapies. I think there's really an unmet need. Directly addressing the APOE 2E4 levels, you can see them as the E4 homozygotes as a separate population with a slightly different, more severe disease. You go into that population with an APOE-based therapy. Even though it's only 10% of the total Alzheimer's population, that's still a substantial group of people. Yeah, so when you have these two approaches for Tau, we've been focusing a lot on Alzheimer's disease. We have to remember that that's just one of several tauopathies. Actually, I don't think there's a bigger target in neuro. If you think about progressive supranuclear palsy as also a tauopathy, frontotemporal dementia, and then if you know that chronic traumatic encephalopathy from repeated brain injury also is a tauopathy, it's a massive set of indications. I would think that for some of those other tauopathies, the knockdown approach might be better because there you don't get that characteristic spread. If the antibody is really trying to impede the spread, then maybe decreasing the expression of Tau would be better for these other tauopathies. There's a whole number of things we can do. Once we get the initial data, we start to get some risk reduction and some signals of positivity. There's so many branch points there. Yeah, that leads to another question I had. Obviously, Alzheimer's is a huge space. The studies there can be quite expensive. You even mentioned going beyond Alzheimer's with these Tau-targeted therapies. How are you thinking about partnering? Is it something you're going to pursue on your own? No way. At what point do you partner? I'd love to hear some context there. We're too small to go it alone on even just Alzheimer's, right? I mean, no, we would want to partner it. Exactly when? I mean, look, we have enough cash to get through the mad Toby's, you know, clinical trial that reads out toward the end of next year. After that would be a good time. I'm open. I'm open to any good ideas that benefit patients and Voyager shareholders. It's too big. It's too big for Voyager to do it alone. Yeah. The good news is we know there's a lot of interest in it. Obviously, large pharma has a bunch of LOE gaps that they need to fill, and this is perfect for a lot of them. Also, many of them are pursuing Tau on their own. You know, Merck, Johnson & Johnson, Eisai, UCB. I mean, we know that Novartis has Tau programs. Lilly has Tau programs. You name it, everybody's targeting Tau. I assume there'll be a lot of interest if we get some positive data. Yeah, and you probably already have a pretty full Rolodex as well, given your partnerships with the TRACER™ portfolio. I guess maybe that's a good transition to talk about the gene therapy side of the business, ex-Voyager with the partnerships. Neurocrine Biosciences, I think, is pursuing two INDs for gene therapies in Friedreich's ataxia and GBA1 Parkinson's disease. I guess those are external programs, but what is your sense for when those INDs could be filed and when we could get initial data from those programs as proof of concept for the TRACER™ capsids? Biosciences is guiding that the INDs are going to be filed this year and that the first in human studies will be next year. We have our own wholly owned gene therapy program, the Tau knockdown, which will have an IND next year and also first in human next year. First-in-human clinical data from the Tau knockdown as well. It'll enter the clinic next year. Getting data might take a little longer time. There is the proffer of external partnerships with Pfizer and Alexion as well. Anything to keep an eye on from those partnerships as it relates to near-term clinical updates? I don't think we have any real updates on the Alexion collaboration yet. We hope to find out soon. Yeah, I mean, that's a capsid license. They take our capsid, they're running with it. They're actually making the, putting their own payload into it. It's arm's length for us a little bit, but you know, yeah, we're always in contact though. Gotcha. Shifting back to Neurocrine Biosciences, because those seem to be the first two TRACER™ capsids that are going to move in the clinic, you've focused a lot of your work in neuroscience, as we've discussed, and targeting the CNS. I know Friedreich's ataxia has implications in the cardiac and the CNS, while GBA1 Parkinson's disease seems to be more CNS focused. I guess, do you see the read-throughs from either one of those programs as more relevant to the Voyager internal programs? How are you thinking about the capsid selection with those two partnership programs? For GBA1, Neurocrine Biosciences has indicated they're going to go after Gaucher's disease, the segment that has neurological problems, as well as Parkinson's. They're going to be looking to see, I believe, whether the enzyme can be secreted and measured in spinal fluid and whether the abnormal buildup and substrate can be reduced. That probably, I mean, for that to happen, then our capsids have to cross the blood-brain barrier and get into the brain. Friedreich's ataxia also affects the brain, but the measurements in the CSF, in the CNS are more difficult. Actually, most of the time, there is a drug approved for the neurological aspects of Friedreich's ataxia, but it's a clinical outcome measure. There's no real good biological measurements, if you will. The irony is that the biological measurements are better made in the heart. You can actually do right ventricular biopsies in the heart. You can measure pump function, left ventricular function. For Friedreich's ataxia, I think many of the readouts are probably going to come from the cardiac side. That doesn't really speak to whether or not the capsid got across into the brain, right? That's how I think about it. What do you think? I think that's right. The GBA-based biomarkers clearly sort of speak to the CNS. The only other comment I make on FA is that Alexion has highlighted a potential path for approval based on cardiac levels of frataxin and cardiac function. Gotcha. Yeah, and Gaucher, there have been gene therapies previously pursuing that indication. It's very clear the biomarker data can evolve relatively rapidly in that space, right? I think so. I mean, it's a rare disease, right? We know it's due to, you get an abnormal buildup of substrate. Some people think this substrate buildup is what's toxic. Others think that's not the real reason. That's a clear-cut measurement that you can potentially go to FDA and say, hey, you know, this therapy's working. Yeah, I guess you invoked FDA. I just want to ask you, what have your recent interactions been with as it relates to the FDA? I know everyone's seen a lot of turnover at the agency. Yeah, so far, we haven't had any effect from that. We're still mostly preclinical, right? I mean, we do have one program in the clinic, but so far, our pre-IND meetings have been pretty much routine, pretty successful. It hasn't affected us yet. Okay, great. I think we only have a minute left here, but I guess to summarize, what points would you bring forward for investors looking to get greater information on the Voyager Therapeutics story as it relates to catalysts? The one thing I did want to touch on too was the cash position of the company. I think you've done a great job of creating external partnerships that have brought in non-dilutive capital. It would be great to highlight that as well. Yeah, I'll start with the cash part. At the second quarter, we have $262 million, which gets us into 2028. That doesn't include a bunch of milestones that we'll hopefully get over, so it'll probably be extended well beyond that. Of course, that cash runway gives us the opportunity to get through next year without a cash overhang. Next year is going to be a big year for us. There's going to be a lot of readouts around Tau. We had one investor tell us, like, I think it's going to be the year of Tau. Look at, we have two programs in Tau. It's going to be a big deal. You've been all over it. You had a KOL call with the Tau expert. When that happens, make sure you write the note saying I was way, you know, advanced. I told you guys about it. Voyager Therapeutics is a great company. Can't preview any research. Okay. Anyway, we're out of time. Anything else to wrap, guys? I know we covered a lot of ground. Thank you.