Voyager Therapeutics at Virtual CNS Forum: Strategic Insights on Neurotherapeutics

Voyager Therapeutics (NASDAQ: VYGR) presented at the Virtual CNS Forum on Wednesday, 19 March 2025, sharing strategic insights into its innovative neurotherapeutics platform. The company highlighted its focus on leveraging human genetics and biomarkers to reduce risk and achieve proof of concept. While optimistic about its gene therapy and antibody approaches, Voyager also acknowledged challenges in program execution and capital efficiency.

Key Takeaways

• Voyager has a cash balance of $330 million, ensuring operational runway into mid-2027.
• Thirteen partnered programs are generating non-dilutive revenue, with INDs for Friedreich’s ataxia and GBA1-mediated diseases expected this year.
• The company is developing a gene therapy capsid discovery platform and a ligand-based platform to cross the blood-brain barrier.
• Voyager aims to become a modality-agnostic neurotherapeutics company, focusing on neurodegenerative diseases.

Financial Results

• Cash Position: Voyager reported a robust cash balance of $330 million, providing financial runway into mid-2027.
• Revenue Generation: Thirteen partnered programs contribute to non-dilutive revenue, supporting ongoing research and development activities.

Operational Updates

• Partnered Programs: Key collaborations with Novartis, Neurocrine, and AstraZeneca Alexion are advancing, with INDs for Friedreich’s ataxia and GBA1-mediated diseases anticipated this year.
• Emerging Platform: Voyager is exploring receptors for drug delivery across the blood-brain barrier, with data on the ALPL receptor expected this year.
• Internal Key Programs: The company is advancing its anti-tau antibody and gene therapy tau knockdown programs, aiming for clinical readouts in 2026.

Future Outlook

• Clinical Proof of Concept: Voyager anticipates significant milestones, including an anti-tau program readout in late 2026 and early biological measure readouts from gene therapy programs.
• Strategic Direction: The company aims to leverage human genetics and biomarkers to de-risk its programs, focusing on capital efficiency and broadening its therapeutic modalities.

Q&A Highlights

• ALPL Receptor: Discussions centered around the role of ALPL in drug delivery and its safety profile, with no dose-limiting toxicities observed preclinically.
• Tau Targeting: Encouraging results from a mid-domain antibody suggest potential efficacy in reducing tau accumulation, with implications for Alzheimer’s treatment.
• Friedreich’s Ataxia: Voyager’s program addresses both neurological and cardiac components, with safety considerations for frataxin overexpression.
• GBA Parkinson’s: The company is optimistic about gene therapy’s potential to modify the disease, particularly with early intervention.

For a comprehensive understanding of Voyager Therapeutics’ strategies and developments, refer to the full transcript below.

Full transcript - Virtual CNS Forum:

Paul, Moderator: Great.

Thanks very much, everybody. It’s my pleasure to be moderating this panel with the Voyager Therapeutics team. With me is Al Sandrock, Toby Ferguson, and Nate Jorgensen. I’m gonna ask Al to provide maybe a three to five minute overview of Voyager, the platform, your key programs, and then Al, we will dive deeper into Q and A. So thanks so much for taking the time, and I’ll let you

Al Sandrock, Voyager Therapeutics: take it away. You’re welcome. Thanks for having us, Paul. So, yeah, so Voyager, we’re a neurotherapeutics company, leveraging human genetics to find the best targets and to use biomarkers to efficiently reduce risk, provide proof of concept. We have two platforms.

One of them is emerging and the other one is more established. The first one I’ll talk about is our gene therapy capsid discovery platform. So here, what we’re trying to do is improve the delivery of AAV gene therapy into the brain by finding novel capsids that cross the blood brain barrier after intravenous injection. It’s not just for convenience. It’s actually a better way to get genes expressed across the central nervous system by leveraging the vasculature.

We believe it’s also safer. And many of the capsids we discovered are so potent, we can go to lower doses and detarget the liver. And I believe we’ve got a lot of good external validation on this platform, because we have great partnerships with people like Novartis, a leader in gene therapy, Neurocrine, a leader in CNS therapy. And we also have a partnership with the AstraZeneca Alexion. And what these partnerships have done is, we have 13 of them and they have provided some very nice non dilutive revenue.

And some of the programs are gonna be entering the clinic soon. I’ll be talking about that in a minute when I talk about our programs. The emerging platform is where we’ve taken the discovery of the receptors that some of these capsids leverage to get across the blood brain barrier. And we’re making ligands against those receptors and to shuttle other types of drugs across the blood brain barrier, much the way people are currently using transferrin receptor to get things into the brain and muscle. And so, that’s an emerging platform.

We discovered a new receptor last year. We announced one of them called ALPL. And, you know, and so we’re excited about that emerging platform, and we look forward to sharing data on that this year. Our two key programs, internal key programs are both centered around tau. The first one, the lead one is actually not even a gene therapy at all.

It’s a regular antibody against tau, the C terminal epitope. We’ve just announced that we completed the single ascending dose study in normal healthy volunteers. And we’re moving to a multiple ascending dose study in Alzheimer’s disease patients. We expect the readout second half of next year in that program. And then we have a gene therapy tau knockdown program where we’re decreasing the expression of tau across the CNS, using AAV gene therapy.

I would just want to highlight two of the 13 partner programs because they’re nearing INDs. One of them is, Friedreich’s ataxia. Our FA program is partnered with Neurocrine. We expect an IND this year. And the other one is GBA1 for GBA1 mediated diseases, namely Gaucher’s and GBA1 Parkinson’s disease.

That IND is also expected for this year. So that in a nutshell is where we are. We have a strong we have a we just announced we have a cash balance of $330,000,000 We have runway into mid-twenty twenty seven.

Paul, Moderator: Yes. Okay. Great. Thank you, Al. So maybe I want to start and ask a couple of platform scientific questions and then we can talk about tau from from multiple angles.

But maybe to start, I mean, I I you brought up the transparent analogy, which was gonna be embedded in my first question. But, you know, maybe for ALPL and, you know, some of the other receptors that I think you haven’t disclosed, but maybe just ALPL specifically, like, what what is its role in the blood brain barrier? And how confident are you that you can actually kind of leverage it without interfering with its endogenous function? I mean, that’s ultimately been the big source of innovation in Transfarent where some of the earlier constructs led to internalization or you can have hematologic issues. And it’s been an iterative process to be able to do that safely now with Denali.

So, where are

Al Sandrock, Voyager Therapeutics: we with your Yeah. So, we are getting more and more excited as data emerge. Already, we know that humans, if you look in the human genetics literature like Nomad, platforms like that, that humans are pretty tolerant of loss of function mutations in ALPL. So for example, heterozygous knockouts, if you will, of ALPL are fine. They’re normal human beings.

So, so that’s I think portends well. I also, I would say that even Denali, the leaders in transferrin receptor are looking at CD98, for example. You might ask, well, why are they looking at a second receptor if the first one is perfect? Well, it’s probably not perfect. And I would just say that each receptor is going to have its own distribution, kinetics and safety profile.

And so I think we may end up needing more than one shuttle for the right situation. We are actually doing head to head experiments right now against transferrin receptor to understand, you know, what are the differences? What are the advantages? And what are the potential disadvantages? But in terms of your first question, which is what is the role of ALPL?

It’s actually unclear. We don’t really know what it’s supposed to be doing, why it’s on the blood brain barrier and what its role is.

Paul, Moderator: Okay. Okay. Well, what have you shown now as it relates to biodistribution and the percent of the capsid that is actually crossing the blood

Al Sandrock, Voyager Therapeutics: brain barrier? Well, we know that if we look at

Paul, Moderator: the

Al Sandrock, Voyager Therapeutics: capsid that leverages ALPL, we get broad brain distribution and spinal cord. So we get and we get very good neuronal and glial cell transduction with that with AAVs directed against ALPL. We all we also like the fact that we know there’s a human homologue for ALPL. So so that portends well that our our capsid will cross species. And that’s no small matter because in this field, turns out that some of these AAV blood brain barrier crossing AAVs are actually very species specific, sometimes even strain specific.

So to know that it acts the receptor is present in humans is actually very comforting.

Paul, Moderator: Right. Right. Right. Okay. Okay.

Very interesting. Anything that you’ve seen preclinically that, again, getting back to this question of targeting ALPL, like anything you’ve seen preclinically that you see as kind of dose limiting or you oversaturate the receptor or something is some sort of endogenous function is interfered with or at this point, have you just not really found anything?

Al Sandrock, Voyager Therapeutics: We just haven’t found anything yet that concerns us. And as I said, we look forward to sharing all that data this year sometime.

Paul, Moderator: Yeah. Okay. Great. Alright. Let’s talk about TAO because you and I did panels where we talked about TAO when you were at Biogen.

And, you know, I think I don’t want to put words in your mouth, Al, but I have a decent memory. And I think your view evolved over time that targeting intracellular tau, you know, with an ASO in that case or, you know, in this case, a gene therapy expressing in this RNA, might be the way to go because the antibody might be restricted to accessing a small percentage out. Where do you stand now on the role of the silencing approach and the antibody approach? And, you know, why do you think both are still valuable in developing?

Al Sandrock, Voyager Therapeutics: Yeah. So, you’re right about that. So, as you know, the Biogen N terminal directed anti tau antibody didn’t work. We were actually not even, you know, it’s published now. And we weren’t able to show even a biological effect.

And there was another N terminal directed antibody by another company that also failed. So, my view of antibodies was starting to, I was getting less optimistic about that approach. Whereas the BIV80 program, which everybody knows about the antisense that knocks down the expression of tau, actually is looking very promising. So, when I came to Borger and I found out that we had anti tau antibodies, I wasn’t all that, you know, enthusiastic about it. But then what I found out was that they were using a really interesting animal model that actually, I think, started in Steve Paul’s lab when he was even when he was an academic before he came to to, to Voyager, where you take human pathological tau purified from Alzheimer’s brains, and you inject it into the mouse that has that’s a transgenic mouse for P301S tau.

And you look at the spread of tau in the animal. And and and, they had a few antibodies that blocked the spread. FORGER did. I shouldn’t say they. I should say we now.

But at the time, I was still not officially in the company. And what was interesting is that the N terminal antibodies that were tested in that same model failed. So that animal model seemed to predict, at least in a negative way, the failure of the N terminal antibodies. That caught my interest. And so, and then, more recently, we found that the, that some of the other domains actually work.

And we had some in the mid domain, some in the C terminal, etcetera. We had actually had about a half a dozen. So we had to choose which one. And we just chose the one that was the most robust and consistent in that model. Now, in the meantime, UCB had a mid domain antibody, and we actually had a mid domain antibody too, that I thought would be the first test of whether it had positive predictive value.

So as I said, the animal model had negative predictive value. Does it have positive predictive value? And we even said before we learned of the UCB results that that would weigh heavily on our decision about what to do with our own antibody. And lo and behold, the mid domain antibody, which we would have predicted would be positive based on the animal model, did show, I think, a pretty convincing effect on the accumulation of tau in humans. So that’s why my interest in, anti tau antibodies has been reinvigorated, if you will, still in early days.

But I don’t want to throw away the notion that an interim that an antibody directed against the right epitope might actually be beneficial for patients.

Paul, Moderator: Right. Okay. So, how far can you take this in a, you know, a sort of capital conservative way to, you know, generate additive data that then, you know, might interest a strategic?

Al Sandrock, Voyager Therapeutics: Yeah. So that’s a that’s a really interesting question. In fact, you know, all of the all the programs we we we are doing now and we seek to do in the future are gonna have a common characteristic of being very capital efficient to get to proof of concept. You know, neuro is still there’s a very high unmet need in neuro particularly neurodegenerative diseases, partly because people haven’t been successful to find drugs that work. So it’s high risk.

But the good thing is that the field is developing biomarkers, both fluid based, blood based, as well as CSF based, and imaging biomarkers that can derisk. So I believe that an effect on multiple biomarkers would be intriguing. Certainly would have been for me if I were still at a large company as a buyer. But I think in a but the key question now is, well, what’s the clinical benefit? And that’s the that’s the part that it took a while, for example, for anti amyloid antibodies.

We had to learn that that you had to have a substantial effect on amyloid burden in order to get a clinically meaningful effect. Right. And that took years with multiple different drugs to learn that relationship between the effect on tau imaging and clinical. And so that’s going to happen because multiple people are looking at that. We expect data even this year as well as next year.

So that, I think, is going to be very helpful. We’re going to pay a lot of attention to that.

Paul, Moderator: Yeah. Yeah. Okay. Makes a lot of sense. And as it relates to that Biogen IONIS data next year, are you optimistic that that’s going to be positive?

And if so, what’s the read through to your gene therapy?

Al Sandrock, Voyager Therapeutics: Yeah. Well, look, I don’t know if Toby’s online and I want to get him give him a chance. Toby, are you on? I guess he’s not. So so I guess I’ll answer the question.

Yeah. I’m pretty optimistic. Look, I mean, the data that they’ve shown so far, particularly as time has gone on, you know, the the the we have to interpret it carefully because there was no control group. Right? So it was a single arm study.

But they have done a great job, I believe, in comparing it to natural history using propensity matching, as well as the control group of an anti tau antibody trial. And in both comparisons, it’s looking very interesting. In fact, the first thing is, surprisingly, you get a decrease in tau expression even in the areas that already had expression. So these tau PET ligands bind to pathological tau, which we believe is in neurofibrillary tangles. Now if you were to ask me years ago, I would have said those tangles are pretty irreversible.

That just by decreasing the synthesis of new tau that they would Right.

Paul, Moderator: Mantle. Kind of like the issue with base and Alzheimer’s. Right?

Al Sandrock, Voyager Therapeutics: Yeah. Exactly. Base didn’t work. Right? Because the the the flocks were were were not removed.

Paul, Moderator: But

Al Sandrock, Voyager Therapeutics: here, it looks like the tangles are going away, which is quite a surprising wonderfully surprising result. And then the second thing is that the effect size, again, these are cross trial, if you will, comparisons, but the effect size looks much larger than the effect sizes we get with the anti amyloid treatments. So so for both of those reasons, I’m actually pretty optimistic, and I wish Biogen well. Yep. Yep.

Okay. Great.

Paul, Moderator: Well, I want to cover a few of your other programs. And I guess on the FA program, which I know there’s some limits to what you can say because it’s partnered with Neurocrine, but maybe just talk about what the target product profile is there. And with your platform, do you think you can simultaneously address the neurological component, sure, the cardiac component? And also with for tax and specifically, right, there’s this pronounced need, I think, to avoid over expression in certain tissues, especially the liver. So maybe talk about the degree to which you think you could throw the needle on all three of those things, which would certainly be the

Al Sandrock, Voyager Therapeutics: best case scenario. Yeah. Okay. Yeah. So, so as you just pointed out, there’s a neurological component and a cardiac component.

The neurological component is disabling even in children, right, and teenagers. And then it’s the cardiac component that ends up being fatal, as they get older. And so both should be addressed. And our AAV, we have AAV capsids that will transduce both heart and central nervous system. So I think that’s a distinguishing feature of the program that we have partnered with Neurocrine.

And so, we aim to have effects, clinically beneficial effects on both cardiac and CNS function. And as you know, there’s a precedent now for a drug to be approved for the CNS side of the disease because Brianna’s drug, which was acquired by Biogen Skyclaris, was approved based on a functional rating scale for free drugs ataxia. So that sets a nice regulatory precedent for that pathway. Lexio has, I think, you know, gotten according to what I read from them, that they have some agreement with FDA on parameters to address the cardiac function, which I believe involves echocardiography, and perhaps fluid based measurements. So I think there’s gonna be a path forward for the heart as well.

And and so the product profile to try to answer your question is gonna need to address both the heart the heart and the and the and the brain, of the nervous system, I should say. The the, safety issue yeah. So overexpressing frataxin seems to be harmful. Now we know also that heterozygotes carriers, which express, you know, 30 to 50% of frataxin are normal. So you don’t you don’t really need to do a lot you don’t wanna express too much.

Right? In fact, 50% would be enough. 50 of normal seems to be enough so that because the carriers are completely fine. So so that that produces a nice slow window. And I don’t wanna talk about Neurocrine’s program, but there are ways to limit the expression, you know, by by doing things in the payload.

Some other companies have leveraged those, and I don’t wanna go too far into that because I might be spilling the beans on what Neurocrine what’s a Neurocrine program. But also, I would say that our capsids are nice in that, you know, what we found out was that when we get BBB penetrant capsids, they tend to detarget the liver. And that’s one of the organs we’re worried about, with Overexpression.

Paul, Moderator: Right. Yep. Okay. Great. Do you want to briefly touch upon GBA?

I mean, I think the rationale in, the rationale in Gaucher is pretty intuitive. But as it relates to GBA Parkinson’s, I think the one thing I’ve wondered with the number of these genetic targets and the answer is not going to be all equal is just like is simply fixing the genetic defect going to be enough or is that, you know, one of the number of biological hits combined with environmental hits. And so I guess maybe I would flip that around on you like with with rescuing GBA, what’s the optimistic case that that’s actually going to have a disease modifying?

Al Sandrock, Voyager Therapeutics: Well, you know, look, I think that Parkinson’s is a heterogeneous disease. I think there’s, as you were kind of pointing out there in some ways, there’s going to be multiple factors, right? And perhaps there’s going to be more than one biological cause, if you will. I do think that there’s a lot implicating the lysosomal pathways as important for Parkinson’s, even in those that don’t have, who are not GBA1 carriers. So, there are lots of other genes that tend to affect the lysosomal pathways, right, the endolysosomal pathways.

And so, and actually that’s not just for Parkinson’s, by the way. I think that endolysosomal pathways seem to be involved in a variety of neurodegenerative diseases. GBA is a way to address the lysosomal pathway clearly in some of these GBA1 carriers, since they have the same allele as in the homozygous case, you get Gauchets, they’re clearly a loss of function alleles, because in the homozygous state, they cause Gauchets, right? So, if we pick those alleles that we’re pretty certain are loss of function by the way, the other way we know that is that the substrate goes up, the substrates for the enzyme g case are elevated because the enzyme is not working properly. So if we pick those patients, I think there’s a pretty decent chance that we can help those patients.

Of course, as always, what stage do you have to get in? Do you have to get in early? And of course, you know, we always say the earlier the better. And, and so I’m pretty hopeful. And the only way to know is to do the human experiment, I believe.

Paul, Moderator: Yep. Yep. Okay. Great. Well, I know you have a number of other efforts ongoing.

You have the non viral ALPL shuttle program. What else would you like to highlight in the last couple minutes, Al, for people to take away here?

Al Sandrock, Voyager Therapeutics: Yeah. I think it’s the fact that we do have this other emerging platform that we’re, you know, we seek to become more of a multimodality or a modality agnostic neurotherapeutics company. Our flywheel is going to be neuro, leveraging, as I said, human genetics, leveraging all the development of new biomarkers to derisk very in a capital efficient manner. I’m growing a great team. It’s too bad Toby couldn’t come on because he’s one example of the great team I’m assembling.

And we have a strong cash balance. You know, we as I said, we ended the year with $330,000,000 in cash, and we have cash into mid twenty twenty seven. So I’m very excited about the company, and I hope you are too. Can’t hear you, Paul.

Paul, Moderator: Yeah. No, I think it’s great. It’s always a pleasure talking to you guys. The science is super interesting. And maybe just to wrap up, like, when do you think you will have clinical proof of concept from some of these new IND programs?

Is there any guidance you can give? Like, as ’26

Al Sandrock, Voyager Therapeutics: are real? We have the guidance that the anti tau program, second half of twenty twenty six. I’ve also said that the neurocurrent programs, both of them, we have IND scheduled for this year. And the only thing I would say without being specific, because those are neurocurrent programs, is that with gene therapy programs, you don’t do normal healthy volunteer studies as we just did with the TAAP program. You have to do studies in patients.

And you have to use doses that have a chance of helping the patients. And so, that provides a potential for fairly early readout, particularly on biological measures that can tell us that the gene is being expressed in the right locations in the brain and elsewhere. So, I do think that, I think 2026 is going to be a great year for us. I certainly hope so.

Paul, Moderator: Yeah. Okay. Great. We’re looking forward to staying in touch, Al. Thank you very much, and thanks to the team as well.

We appreciate it. Thank you. Alright. Talk to you guys

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