Hello, everyone, and welcome to the fifth annual H.C. Wainwright Virtual Neuro Perspectives Conference. My name is Patrick Trucchio, and I'm a senior healthcare analyst at H.C. Wainwright. I'm your host for today's event. We have an exciting agenda at the conference this year, with more than 20 companies presenting, with their sessions available on demand through the conference portal. In addition, we are expecting a full day of panels and fireside chats on the day of the conference, June 27th, with a broad neurology focus across many indications, from depression and epilepsy to Alzheimer's disease and ALS, along with novel methods of drug delivery to the CNS. This is by far our strongest agenda ever.
With that, it's my pleasure to introduce our next speakers, Todd Carter, CSO, and Trista Morrison, Chief Corporate Affairs Officer and Chief of Staff to the CEO of Voyager Therapeutics, a biotechnology company dedicated to leveraging the power of human genetics to modify the course of, and ultimately cure, neurologic diseases. To start, maybe we can begin with some background on Voyager, including the platform that underpins the pipeline.
Maybe I'll start and then pass it off to Trista, as well. But first, I'd like to say thank you for the invitation to join. Quite excited to be part of the conference and have the opportunity to discuss everything, so thank you. So at Voyager, our focus is really on neurogenetic medicines, and around that, we have a pipeline of four wholly owned and 13 partnered programs. The first of those is our antibody. It targets a pathological form of tau in Alzheimer's disease, and we entered the clinic last month. In addition to that, we have the potential for three more gene therapies to follow in 2025. On the platform side, our TRACER novel capsid discovery platform is really what is enabling these gene therapies.
One of the major challenges of treating central nervous system gene therapy, central nervous system disease, has been delivery. That's the ability to really get the therapeutic we want to deliver to the right part of the CNS. At Voyager, we've developed an industry-leading platform that can overcome these challenges, and that's our TRACER platform. It enables us to develop and discover novel capsids that, with an intravenous delivery, so into the bloodstream, we can harness the vasculature of the CNS to deliver broadly across multiple brain regions and cell types throughout. These capsids have demonstrated translatability across multiple species, that includes rodents, it includes non-human primates and different non-human primate species.
And that cross-species activity really gives us confidence in the ability to translate into humans as well, and that's what's really enabled the selection of these three development candidates in our wholly owned and partnered gene therapy programs. And I'd like to think this isn't just our own assessment. We have partnerships with some significant players in the space, around our novel capsids and our programs, and these include Neurocrine, Novartis, and Alexion, and some of those, we've even increased. So we had partnerships and collaborations with them, and they've doubled down, and we've expanded those partnerships. Maybe Trista, I'll hand it over to you to talk about the kind of where we're going and some of the future.
Sure. Thanks, Todd, and thanks, Patrick, for having us here today. I might just add that due to, due largely to those partnerships, Voyager is also well capitalized. We ended the Q1 with just over $400 million on the balance sheet, and that provides us a runway into 2027. And what that allows us to achieve is we anticipate several important clinical inflection points during that window. Todd mentioned that our lead pipeline program is VY-TAU01, which is an antibody targeting tau for the treatment of Alzheimer's disease. That's currently in a phase 1 study, and we anticipate having some initial tau PET data that should be able to, to really show us if this molecule is able to inhibit the spread of tau through the brain. We expect that data in the second half of 2026.
In addition to that, as Todd mentioned, we do have three gene therapies that are on track for IND filings in 2025. And while we haven't given any guidance on timeline to data for those, I will note that because they're gene therapies, each of them is going to go into a patient population at a therapeutic dose. So we do believe that, you know, it shouldn't take us too long to see, to see some interesting data out of those studies as well. So a lot of exciting value inflection points coming, and we're well capitalized to reach them.
Right. Great. That's a really helpful overview. Now, Voyager also presented new data at ASGCT 27th annual meeting recently. I'm wondering what the take-home messages were from that for investors.
Yeah, so ASGCT this year was really exciting for us. We had 12 presentations across a variety of different datasets. We covered clinical translatability, manufacturing, and overall performance of our TRACER capsids at the conference. The key, I think of it as the CNS BBB, or blood-brain barrier, session was really full. It was entirely full, actually. It was a line out the door, and it was quite exciting to see that interest that I think the whole field has in delivery to the CNS. One of the key things that I think we showed was our second-generation capsids, and that our second-generation capsids, we've continued to enhance the ability of AAV to get across that blood-brain barrier. We showed improved delivery into the brain and CNS in general.
We also showed a reduced liver delivery. So really, it's that therapeutic window of delivery to the target tissue or the target cell types of interest, and reduction to delivery to what we think of as off-target tissues that is important for the therapeutic window and the ability to use these capsids as therapeutics. By doing so, we were able to see really robust transduction. We could see 50%-75% of cells in different brain regions transduced, which is a pretty high level of transduction, of delivery. In particular regions, in particular cell types, we saw even higher than that.
We were able to see 95% transduction in cell types such as Purkinje neurons, 98% of dopaminergic neurons of the substantia nigra, which is a key region important for Parkinson's disease, for example, and over 80% to spinal motor cord neurons. And this is all at what we think is a very clinically relevant dose of about 3 × 10^13 vector genomes per kilogram. In that context, we also presented on our SOD1 ALS and our tau knockdown programs, both of which are highly validated CNS targets. On our SOD1 ALS, we showed how the novel capsid enabled the selection of our development candidate that we were talking about earlier, both Trista and I mentioned it.
So we did these studies in non-human primates, and with the ability to target 80%-90% of motor neurons in the non-human primates, all of this following a single intravenous dose, we saw 80+% knockdown of SOD1 in those target cells. That's an extremely high level of knockdown, and important for mediating the efficacy that we hope to see in the clinic. We also know that we can deliver not just to the spinal cord after the intravenous dose, but also more broadly in the CNS, including the brain stem and the motor cortex. So we're able to deliver to multiple different cell types and regions using IV delivery.
For tau, we showed proof-of-concept data in a mouse expressing human tau mRNA, that we can reduce tau mRNA 70%-85% in the brain following a single intravenous dose, with the blood-brain barrier-penetrant capsid in one of our payloads. Again, this is all after a single IV dose, in a system where we can look at the tau mRNA. Finally, we also presented and described for the first time, the identification of a receptor responsible for the BBB penetration. This is a protein, it's a receptor called the tissue-nonspecific alkaline phosphatase, or ALPL. That's a highly conserved receptor, highly conserved in these species, where we're seeing the cross-species activity.
It's also very highly conserved in humans, and the importance of that is, not only do we now have a greater understanding of how these capsids are getting across the blood-brain barrier, but we can show that the capsids are binding these receptors with the non-human primate forms, the rodent forms, and we can show it binds the human form of the protein, and that human form also mediates the right things in in vitro studies. All of this really increases the confidence that we have the potential for translatability in human beings in the clinic. So, I guess, fundamentally, the main takeaway here is that we have TRACER capsids that have enabled the selection of these multiple development candidates, all off of these second-generation capsids, both in our wholly owned and our partner gene therapy programs.
Right. Right, all, all interesting and, and helpful. And, maybe we'll move next on then to Alzheimer's disease. Presumably, you know, we assume much of the audience has some familiarity with AD, but just to level set the discussion, can you provide some background on AD, how significant the unmet need is, and where you see potential to differentiate from the field?
Yeah. So Alzheimer's disease is actually at a really, I think, a really critical point. So it's both incredibly exciting, in that, for the first time, starting a couple of years ago, there are disease-modifying therapies that have been approved with the anti-amyloid antibodies. This is a huge advancement for the field and for Alzheimer's disease, and I think really give patients hope. On the other side is, that there is still a really significant unmet medical need. These anti-amyloids work in maybe a third of the patients. There are both responders, partial responders, and then finally, non-responders. But we also know about the biology, I'll call it the pathobiology of Alzheimer's disease. So, we're at a really exciting time for Alzheimer's disease.
With the anti-amyloid antibodies, for the first time, what we're seeing is that there are disease-modifying therapies that have been approved. This is really exciting and gives patients a lot of hope, but there is still significant remaining unmet medical need, because there are not only responders, but partial and non-responders to these treatments. What we know from the pathobiology of the disease is that the amyloid buildup happens earlier in the disease, but then how pathology begins to spread from one part of the brain and more globally throughout the brain.
The hypothesis is that if we can block that spread of pathological tau, which ultimately is what correlates with the disease progression and the cognitive progression of the disease, then we hope to have an effect on the disease itself. Tau remains a really important and validated target, such that so important for us, that we actually have two programs targeting it.
Right. No, that, that's helpful. And just starting with VY-TAU01, maybe you can talk a bit more about the mechanism of action, and a bit more about what the implications are of possibly slowing the spread of tau.
... So for our tau antibody, which is one of our programs, Trista mentioned earlier that that's currently in a phase 1 trial in a single ascending dose. Here, what we've identified is an antibody that binds a pathological form of tau. We target the C-terminal region. We're excited about it, because in our studies, we identified actually a number of antibodies across the tau protein. We filtered them down by looking at those that bound pathological forms of tau, those that are found in Alzheimer's patient brains. And we identified those that removed this what we call the seed-competent forms of tau. These are the forms of tau that have been implicated in this spread of pathological tau through the brain.
We used, in particular, an animal model, where we can take pathological tau from Alzheimer's patients, inject it into a mouse brain that expresses human tau, and then when we do that, we can see pathological tau spread in that mouse brain. We did studies with multiple antibodies across the protein, and the antibody that we chose, we selected, was able to reduce that spread of pathological tau induced by Alzheimer's patient pathological material by up to 70%. And so in this kind of model, the N-terminal antibodies, which have already been in the clinic and have been shown not to work in Alzheimer's disease, did not inhibit the spread. And so we chose this based on the validity of that, and potential for that model, and to represent what's going on in the clinic, and the strong activity that our antibody has in that model.
Right. Can you talk more about the phase 1a trial design? This is evaluating VY-TAU01 in healthy volunteers. What data would you need to see here to support advancement of the program?
So a phase 1 trial, you know, our phase 1 is, I think, fairly typical of a monoclonal antibody phase 1 trial. It's a single ascending dose trial in healthy volunteers. We have a single site where we're expecting to enroll approximately 48 participants or so. And of course, the primary aim is to generate initial safety and PK data that will then give us information to inform the subsequent multiple ascending dose trial. So really, that's the aim for that study.
Got it. And then I think for the next stage of this program, you'd have that initial Tau PET imaging data in the second half of 2026. Can you talk about, I guess, this next stage of the program, and what you would need to see in that data to then give confidence to move the program ahead?
So the clinical development plan for that program is not fully finalized. But I can say a couple of things. One, we do expect and intend to enroll patients with early Alzheimer's disease. So we're looking for... We'll likely be looking for patients that have some tau pathology in the brain. Fortunately, because of the new PET TRACERs that enable us to visualize this through PET imaging, we're able to select patient population in patients at particular stages. So likely around Braak stage 2 is where we'll start. That's a stage at which the tau pathology is present in the entorhinal cortex, but hasn't really spread beyond it. And then what we'll be able to hopefully do then is look for evidence that our monoclonal antibody is able to slow the spread to other parts of the brain. What we're expecting or hoping to have are data on a subset of patients that we can maybe talk about in the second half of 2026.
Right. Great. Can you talk a little bit more about the tau silencing gene therapy? This is the vectorized siRNA program. What's the status of this program?
Yeah. So it's earlier than our monoclonal antibody, but it's a program we're particularly excited about. The tau antibody program binds a particular... That antibody binds a particular epitope on tau. The tau knockdown approach reduces all forms of tau, and what we're looking at right now is BIIB080, which is an ASO that's intrathecally delivered. It's a Biogen program, and they're seeing pretty exciting, although early evidence in clinical trials, that knocking down tau, using this repeat administration method of an ASO, is giving a pretty strong signal on these PET imaging studies, indicating a slowing or maybe even a reduction in the pathological tau burden in those patients. And that's looking like it's correlated with a cognitive benefit as well, so for the mechanism, it's pretty exciting.
So our tau silencing gene therapy is really a different way of delivering a very similar mechanism, where we're knocking down the tau mRNA, and then subsequently, the protein, only we will be doing it with an AAV vectorized siRNA form. So we'll be able to dose a single time, dose once, with an AAV using our TRACER novel capsids to deliver broadly throughout the CNS, knocking down the tau mRNA and then the protein. We have ongoing studies, and right now, we're hoping to file an IND in 2026 for that program.
Got it. And then just moving over to the anti-amyloid beta gene therapy. This is a vectorized antibody program. Can you talk about this program in more detail, and what's the status of this program?
So we think a vectorized anti-amyloid gene therapy could offer some benefits, focused around providing a similar disease-modifying efficacy that we're seeing with the monoclonal antibodies, the anti-Aβ antibodies, but doing so after a single dose. The other component is there's the potential for an increased therapeutic risk-benefit ratio, and what I mean by that is, one of the risks of amyloid antibodies is something called the amyloid-related imaging abnormalities, or ARIA. This seems to be involved in the antibodies binding the plaques on the vasculature in the brain, and seems to be associated with and when you dose an antibody, a monoclonal antibody, through an intravenous administration, you get peaks and valleys of that delivery of that drug, that therapeutic.
With the gene therapy, we're going with a single IV dose, but we're delivering a payload to the CNS, that should then result in a constitutive level of expression of the anti-amyloid antibody. So in that case, we shouldn't have these peaks and troughs. We should have a constitutive constant level, and so there's the opportunity that we're going to avoid some of the peaks that could drive some of the risk of ARIA. But we're continuing... This is relatively early stage, and we're continuing to conduct these early research studies in the program, and looking forward to sharing data at future conferences.
Okay, great. Then maybe moving on to ALS, so just on SOD1 ALS. Maybe you can start by talking a little bit more about this disease area, including the unmet medical need.
So SOD1 is a very well validated target for SOD1 ALS. Of course, SOD1 is a gene. There are toxic gain-of-function mutations that occur in familial forms of ALS. It's been shown to be a causative gene, and recently, a drug called tofersen has been approved that, in a similar fashion to what I described for BIIB080 or tau, only tofersen has been approved in an accelerated approval mechanism. It's an ASO that's delivered intrathecally as well. Has to be repeated, but it knocks down SOD1 at the mRNA level, and what has been shown is that has a strong efficacy in SOD1 ALS patients. So we're taking a similar approach to that tau, where we have identified a vectorized siRNA that knocks down SOD1 intracellularly.
We can use our IV-delivered BBB-penetrant capsids, and there, we have already selected a development candidate. As I mentioned before, we're able to reduce SOD1 expression in the spinal cord motor neurons by upwards of 80%. We can hit these other brain regions, and what we're hoping is that that should have the potential to provide a single-dose disease-modifying treatment with that gene therapy.
Right. Interesting, and then, just regarding VY-9323, this is the vectorized siRNA, maybe talk a little bit more about the mechanism and how it's differentiated.
Right, so the mechanism in compared to tofersen is similar. It's knocking down an mRNA. There are some subtle differences as to exactly that mRNA knockdown, but effectively, it's a very similar approach. We do think it's differentiated via some of the other approaches that are out there, in that it's a single dose, so a one-time dose that should persist. It's also an intravenous dose, so it doesn't require a direct administration into the CNS. That gives us the advantage of it can be a simpler administration, and it also harnesses the vasculature of the brain to really distribute it widely. And because of that broad distribution, we're able to not only deliver to the spinal cord and the motor neurons there, but also these other parts of the brain. So I think those are all important aspects of our VY-9323 approach.
What's the status of the VY-9323 program? When are the next updates expected?
Yeah, Trista, do you wanna take that?
Sure, yeah. So earlier, when I said that we have three gene therapies that are marching towards an IND in 2025, this program is one of them. So, VY-9323, our SOD1 ALS gene therapy, that is a wholly owned program, and we are tracking to file an IND in mid-2025 for that program. Now, we have not yet disclosed the clinical development plan and when we would see data, but again, as I referenced earlier, because this is a gene therapy, it- there's no healthy volunteer study here, right? Like, after we file that IND in mid-2025, this program will go into SOD1 ALS patients, and it will go at therapeutic- what are anticipated to be therapeutically relevant doses. So how long will it be until we see some meaningful data out of that? I... You know, I'm not gonna say that it's gonna be the first patient.
I think, you know, our company is... Our CEO, we're not a big fan of necessarily, you know, doing a press release or making an announcement on, like, every single patient, but 'cause we like to see things repeated. But I think that it probably won't take too many to see something interesting, if everything goes well. So that's what we're looking forward to.
Right. Interesting.
The other two, just to complete the initial, when we talked about the three gene therapies going into the clinic in 2025, the other two are Neurocrine partnered programs for Friedreich's ataxia, and GBA1 for Parkinson's disease, and other GBA1-mediated diseases.
Great, and it's a, I think, a good segue, because we wanted to ask about the partnered programs. And maybe you could talk more about the partnered programs and, you know, understanding that, you know, the, the visibility here may not be, you know, directed as much through Voyager, but when, when might we expect the next updates on, on those programs?
Yeah, I mean, I can start with that, and then Todd, maybe you can, you know, fill in if I miss anything. As Todd mentioned earlier, we do have 13 partnered programs, so, there's a lot going on in the partnered pipeline. All of those are gene therapy programs, and they all leverage our novel TRACER capsids, which are IV delivered, and then harness the vasculature to cross the blood-brain barrier. So, I think, you know, maybe two points that are important about the partnering strategy and the partnered programs. One is that as Todd mentioned, you know, we were really excited to see two of our partners double down on their partnerships, right? So you had Neurocrine, who had a partnership with us dating back from 2019, and then you had Novartis.
They had a partnership with us, and in both cases, in early 2023 for Neurocrine, in early 2024 for Novartis, in both cases, those partners decided to sign new partnerships with us, looking at additional programs and additional targets. And I think that's exciting because if you think about it, they were already under the hood, right? They were, they were already working hand-in-hand with our teams. They already had our capsids and our technology in their labs. They, they were as close as you could possibly be to what we're doing. And so the fact that they then decided to increase the size and the scope of the partnership with us, that they wanted to go deeper, I think that that speaks volumes. So we were very, very excited about that.
The other point I'll make is that across the 13 partnered programs, we have upwards of $8 billion in potential milestone revenue. And I... You know, I get it. Some of that is, you know, commercial milestones, and we're in a high-risk area where some of that may not be realized, but I will note that some of it is already becoming real, right? Earlier this year, we and our partners at Neurocrine, through the Joint Steering Committee, nominated a development candidate for that GBA1 program, and we nominated a development candidate for the FA, the Friedreich's ataxia program, right? So both of those triggered milestone payments to us. So they're small, but that's real revenue that's starting to be realized.
Of course, the hope is that as those programs progress and as additional programs progress, both with Neurocrine and with Novartis and with Alexion, right, that that starts to become a pretty meaningful revenue stream over time. And in addition to that, we also maintain the right to opt in on the GBA1 and the FA program, and do a co-promote option on both of those in the U.S. only. So we'll be excited to look at that when the data come as well.
Right. Terrific. Well, I think maybe one more question. Just what do you think investors are missing about the Voyager story?
Gosh, do you want me to go first?
Yeah, why don't you go first, Trista?
Okay. I think, No, I think from my standpoint, I think it's really just how many potential clinical inflection points we have coming up over the next 1 to 2 years, right? I think a lot of folks are really anchored on the second half of 2026, and when we get that, when we anticipate getting the tau PET imaging data for VY-TAU01, for the antibody, because that one is the only one that is already in the clinic, and we have definitively provided guidance on when we expect to see that data, right? But I just think it's really important to recognize that this is not a binary story, right?
We also have these three gene therapies moving towards IND in 2025, and as we talked about, there is a potential to see some clinical data from those in a relatively short timeline after they enter the clinic. And then we have things coming beyond that. Todd referenced the vectorized tau knockdown program for Alzheimer’s disease. We're anticipating an IND in 2026 for that. So I think there's a lot of a lot of potential value inflection points coming up.
And maybe I'll add, from my point of view, one thing that I'm really excited about is the receptor. So I mentioned earlier the receptor that enables the BBB penetrance for some of our capsids, our key capsid families. And that's really important, and I mentioned how important it is in giving us confidence in that translation, that cross-species activity into what we think should work in human beings. All that is really important. In addition to that, though, we also here have the opportunity to maybe use that receptor to harness it, to get non-viral things, things other than AAV gene therapy across the blood-brain barrier. At the beginning of this, I mentioned how CNS delivery has been one of the biggest challenges for the field, and that AAV solves aspects of that.
This receptor and our ability to go after it also could potentially solve that particular challenge in other ways as well, and across different modalities. And, we believe that non-viral platform would nicely complement our TRACER capsid discovery and broaden the potential impact for patients and our opportunities in this space and across different modalities.
Right.
Yeah, that's a great point, Todd. I mean, it really brings it full circle to the point you made at the beginning about neurogenetic medicines, right? That's really what we're focused on. And so whether we're using a viral approach or a non-viral approach, ideally, we wanna be able to match the right modality to the right target and create these neurogenetic medicines that are really gonna be able to cross that blood-brain barrier one way or another and make a difference for patients.
Right. Awesome. Well, it's a really exciting time at Voyager, so we really appreciate you attending our conference and having this discussion with us. I'd like to thank Todd and Trista for having this Q&A with us today. I'd like to thank Voyager again for attending, and all of our attendees for joining us at our fifth annual Neuro Conference. Thank you very much. Have a great rest of your day, a great rest of your conference. Thank you.