Hello, everyone, and welcome to the sixth annual H.C. Wainwright NeuroPerspectives Conference. My name is Patrick Trucchio. I'm a Senior Healthcare Analyst at H.C. Wainwright. We have a robust agenda at the conference this year, with more than 30 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16 for the in-person portion of the conference. With a broad CNS drug development focus across multiple indications, from depression and epilepsy to Alzheimer's disease and ALS, and featuring 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 presenters: Al Sandrock, CEO; Toby Ferguson, CMO; and Nate Jorgensen, CFO of Voyager Therapeutics, a clinical-stage neurotherapeutics company advancing genetically driven medicines for serious CNS diseases.
Voyager's pipeline includes multiple programs starting in tau, a gene therapy pipeline enabled by next-generation capsids, and 11 partner programs with companies including Novartis and Neurocrine. First, if we could start, maybe you can provide an overview of Voyager's strategy, including how your move into multiple modalities of neurotherapeutics, including antibody, gene therapy, and receptor-mediated delivery, sets you apart.
Oh, thank you very much, Patrick, for inviting us, and very happy to be here with my colleagues, Nate and Toby. Yeah, our strategy is to leverage genetics to treat neurological diseases. We go after validated targets, and we view human genetics as a high level of validation. What we're trying to do is to get better delivery into the brain. The blood-brain barrier is still an issue for everything except small molecules. The problem is that if you're limited to small molecules, there are a lot of targets that are not accessible to small molecule drug development, or that's very, very difficult. We like to leverage other modalities, proteins such as antibodies or enzymes, gene therapy, of course, with AAV, and oligonucleotides.
The problem with those last three modalities is that they do not get into the brain very well with systemic delivery, and that limits its efficacy, may create safety issues. Of course, it is a huge inconvenience and burden on the healthcare system, inconvenience to patients. We are experts in delivery, and we want to treat these diseases in a better way, regardless of modality.
Right. Voyager has recently emphasized capital efficiency and biomarker-driven de-risking. How do you define clinical and platform success across your pipeline?
We define success as developing truly differentiated medicines with a transformative benefit. We do not choose programs unless we see a path forward where we can efficiently de-risk the programs in the clinic. We require that not only that the targets are validated, but that there are biomarkers available that can help us de-risk the programs.
Right. Your partner, Novartis, has had tremendous commercial success with ZOLGENSMA. What do you think made that program so successful, particularly as others in gene therapy have struggled? What lessons from that experience are most relevant as you scale Voyager's pipeline?
Yeah, ZOLGENSMA is, I would note that it's an IV-delivered gene therapy. And so, but it only works.
Hello, everyone, and welcome to the sixth annual H.C. Wainwright NeuroPerspectives Conference. My name is Patrick Trucchio. I'm a Senior Healthcare Analyst at H.C. Wainwright. We have a robust agenda at the conference this year with more than 30 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16 for the in-person portion of the conference. With a broad CNS drug development focus across multiple indications, from depression and epilepsy to Alzheimer's disease and ALS, and featuring 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 presenters: Al Sandrock, CEO; Toby Ferguson, CMO; and Nate Jorgensen, CFO of Voyager Therapeutics, a clinical-stage neurotherapeutics company advancing genetically driven medicines for serious CNS diseases.
Voyager's pipeline includes multiple programs starting in tau, a gene therapy pipeline enabled by next-generation capsids, and 11 partner programs with companies including Novartis and Neurocrine. First, if we could start, maybe you can provide an overview of Voyager's strategy, including how your move into multiple modalities of neurotherapeutics, including antibody, gene therapy, and receptor-mediated delivery, sets you apart.
Oh, thank you very much, Patrick, for inviting us, and very happy to be here with my colleagues, Nate and Toby. Yeah, so our strategy is to leverage genetics to treat neurological diseases. We go after validated targets, and we view human genetics as a high level of validation. What we're trying to do is to get better delivery into the brain. The blood-brain barrier is still an issue for everything except small molecules. The problem is that if you're limited to small molecules, there are a lot of targets that are not accessible to small molecule drug development, or that's very, very difficult. We like to leverage other modalities, proteins such as antibodies or enzymes, gene therapy, of course, with AAV, and oligonucleotides.
The problem with those last three modalities is that they don't get into the brain very well with systemic delivery, and that limits its efficacy, may create safety issues, and of course, it's a huge inconvenience and burden on the healthcare system, inconvenience to patients. We're experts in delivery, and we want to treat these diseases in a better way, regardless of modality.
Right. Voyager has recently emphasized capital efficiency and biomarker-driven de-risking. How do you define clinical and platform success across your pipeline?
We define success as developing truly differentiated medicines with a transformative benefit. We do not choose programs unless we see a path forward where we can efficiently de-risk the programs in the clinic. We require that not only that the targets are validated, but that there are biomarkers available that can help us de-risk the programs.
Right. Your partner, Novartis, has had tremendous commercial success with ZOLGENSMA. What do you think made that program so successful, particularly as others in gene therapy have struggled? What lessons from that experience are most relevant as you scale Voyager's pipeline?
Yeah, well, so ZOLGENSMA is, I would note that it's an IV-delivered gene therapy. And so, but it only works, it's only approved for infants up to age two years old. And so the blood-brain barrier changes and precludes its use with IV delivery in older people. That's probably why Novartis did a deal with us on SMA to improve delivery in older people. But yeah, I mean, but ZOLGENSMA, you know, it goes after a very well genetically validated target, a single gene disease. ZOLGENSMA is a transformative treatment. I mean, it's transformative for the patients and the families. And there was a pretty rapid path to approval, so a pretty efficient path to approval. In fact, for SMA now, there is a well-laid out regulatory and development pathway. So hopefully, we will reproduce what we saw with ZOLGENSMA with other targets of similar types.
Right. And then just moving on to the Alzheimer's field, Voyager has three Alzheimer's programs in its pipeline. How do you view the Alzheimer's field today? What do you see as the key unmet needs, and how is Voyager addressing them?
Yeah, so you know, I think the way I look at Alzheimer's, we just started getting the first disease-modifying treatments. I mean, it was a breakthrough to get the first disease-modifying treatments to patients, I believe. It reminds me a lot of MS, you know, in the old days with MS, the first treatments were only about 30% effective. But we've got better and better, and now we have truly transformative treatments for MS and multiple types of treatments. I hope we get there with Alzheimer's disease as well. We believe that the next target to go after, and we think it's well validated, is tau. For that reason, we have two programs against tau, an antibody, a regular antibody that has not been optimized for delivery, to be honest with you.
We have the option to do that later, of course, if we get proof of concept. We have a gene therapy knockdown approach.
Right. So in your programs targeting amyloid and tau, how do you see these two approaches fitting into the treatment landscape?
I believe that just like oncology uses multiple drugs, either in sequence or in combination, we may get to that point with Alzheimer's disease as well. That is why I think it's useful to have more than one target and more than one treatment paradigm. Ultimately, it'll be personalized depending on how patients respond to the first treatment and whether they're complete responders or partial responders.
Right. And then just moving on then to the anti-tau antibody program, VY7523, now in a phase I-B multiple ascending dose trial in early Alzheimer's disease. What are the goals of this study, and what data should we expect in the second half of 2026?
Toby?
Thanks, Al. Thank you, Patrick. To remind, 7523 is our anti-tau antibody program. It's in a multiple ascending dose program. I think what we've learned, particularly from some recent discussions, is that the most relevant readout is tau PET. We'll see that in the second half of 2026. I think the point I make there is there's been some exploration of fluid biomarkers in the field, but some recent discussions at AD/PD, for example, highlighted potential discordance between fluid biomarkers and tau PET. We really are focused on tau PET as the key readout. Of course, we'll explore clinical scores like CDR-S um of B oxes, and fluid biomarkers, but the study formally is really looking at tau PET as the key readout. I'd also highlight that the bepranemab data and really the idea that you can move tau-PET with an antibody was an important learning.
Both the AD/PD discussions and the bepranemab discussions really highlight the importance of tau PET.
Right. I mean, your preclinical data, VY7523, showed potent inhibition of tau spread and superior target engagement in a tau seeding model. Can you walk us through that model and what makes it translationally relevant?
Fundamentally, I think there are lots of ways you can try to choose an antibody to see if it impedes the biology of tau. I think at Voyager, we think the fundamental issue is in humans. We know that tau starts in a localized region of the temporal cortex and the anterolateral cortex. With confluence of beta amyloid, you get this spread of tau. We know that's what correlates with clinical signs and symptoms and disease progression. Really, we think it's that biologic process of tau spreading that is critical to disease. Why we like the P301S model is what's done in that model is on the background of the tau P301S mutation, you inject purified human pathologic tau into the mouse and you watch it spread.
Fundamentally, what we showed with our antibody is that in this model, we could inhibit substantially that tau spread. I think also quite importantly, and really what got us quite interested in this approach was that there have been two prior failures of internal antibodies. In those cases, both of those antibodies also failed in the model. We really like this model because we think it emphasized that process of biologic spread, which we think has potential translatability in humans. I'd also highlight that the propanamab data, their antibody from UCB, worked in this model as well. Some potential partial positive read-through as well.
Right. You noted that the field has struggled with the N-terminal tau antibodies. How is your C-terminal approach differentiated? What are the advantages of targeting that epitope?
I think fundamentally, our epitope, I think the key point that we make is one, the epitopes are different. N-terminal versus C-terminal, and just highlighted our preclinical data in the 301S mouse. I also think a key point is that our antibody is pathologic tau specific. It's really a key point of differentiation. I think the other is based on what we've seen in the field holistically. We think we can explore, based on the safety, quite high doses. I think there's potential differentiation there as well.
Right. You have mentioned learnings from the bepranemab's readout. What are your takeaways from that program? What other programs do you see as potentially having a read-through?
I think the bepranemab data, I think, was certainly a positive step forward for the field. It showed for the first time that an antibody to tau in a human being can impede the accumulation of tau pathologically as measured by tau PET. An important first step. They also showed they missed their primary endpoint on CDR-Sum of Boxes, but they showed in the whole population that you could potentially have an effect on ADAS-Cog, a measure of cognitive performance. I think missing the primary did engender some skepticism in the field. I think fundamentally, the question the field is struggling with is what is the appropriate exposure you need of a tau antibody to get a full clinical effect on measures like CDR-Sum of Boxes. I think there are some coming readouts that will certainly help with that.
I'd highlight there's a pathologic tau antibody for Merck. We'll have some fluid biomarkers readout of that in July, hopefully. I'd highlight the J&J readout and the BIIB080 readout in 2026 that will move the tau field forward holistically. The J&J study is an antibody in a large phase two study that will have appropriate power to look at clinical endpoints. Really understanding that exposure response is a key next step for the field. We really think our antibody is nicely differentiated for pathologic tau. It really has a good chance of impacting this in humans potentially.
Great. Maybe then moving on to the tau silencing gene therapy. This is the VY1706 program. It's a vectorized microRNA therapy delivered intravenously with a TRACER capsid. Can you just maybe provide some background on this program and then walk us through your most recent non-human primate data?
Certainly. I'd refer the group. We had a nice oral presentation at ASGCT in 2025, so that's available. I think fundamentally, the concept here is different than the antibody. Really, the goal here is to sidestep the question of what are the appropriate pathologic species of tau and take a more general approach and knock down tau in cells in the nervous system to decrease overall tau burden. What the team has done is generated this microRNA to do just that. I think what we're really excited about is we've shown in primates with an IV dose of about 1.3 E13, that we have knockdown of up to 73% in the primate tissue. We get, just to emphasize, substantial knockdown throughout the CNS up to 73% at a low dose of 1.3 E13, and that's IV.
We feel that we can move this as a key program to see can IV approach really broadly reduce tau in the human nervous system. So quite excited by it.
Right. What are your expectations for durability and how do you benchmark this program against ASO approaches like BIIB080?
I think fundamentally, this program is meant to be a one-time IV administration. The expectation is that you'd have continuous production of this microRNA, therefore long-term knockdown of tau. Of course, we'll need to do the studies, and the studies will be long-term to determine this, but our expectation is this will be a one-time treatment. I think fundamentally, the benchmark will be the knockdown and responses seen in the ASO approach BIIB080. What they've shown is that you can get about 60% reduction in the CSF compared to baseline. I think that's sort of the biomarker-based benchmark. They've also shown in their studies, phase one studies, that you can see you have baseline pathologic tau as evidenced by tau PET, and some of that can be removed. I think those two things are really the biomarker-based benchmark we'll be aspiring to.
That being said, I think with our single IV administration based on preclinical data, where we see quite substantial reductions of both protein and message, that we think we can meet this benchmark.
Right. What's the timeline for IND submission? What studies remain before filing?
What we've communicated is that the IND will be in 2026. And really, we're in the process of working through the IND enabling work, particularly toxicology, to support that IND or CTA submissions in the U.S. and Canada in 2026.
Great. And then VY1706 and VY7523 target different forms of tau, one extracellular, one intracellular. How are you thinking about the potential for sequential or combination use?
Toby, do you want to take that?
I'm sorry, Al?
I said, Toby, do you want to take that?
Sure, I'll take that. I think fundamentally, I think back to Al's prior point, both with amyloids, anti-amyloid-based therapies and potential different tau-based approaches, antibody or knockdown, I think you're going to need multiple options. I think at the highest level, you're going to understand some patients who respond differentially to antibody, tau antibodies as much as they could to beta amyloid therapies. For example, in someone who you catch relatively early in progression, who has the presence of tau, but more limited spread as evidenced by tau PET, may be an excellent candidate for an antibody approach. Someone who has more widespread tau spread may be appropriate for knockdown. Or you may need a combination of antibody and knockdown simultaneously. You also probably want to sequence the beta amyloid somewhere before these.
I think fundamentally, over time, we're going to learn about different sets of responders to each of these therapies. I also highlight that the safety of these approaches will be taken into consideration. I think really you're going to need this optionality for full treatment of Alzheimer's disease as an entity. I really think it's going to be important to have both options available for patients.
Right. Just earlier in the discussion, talking about the importance of crossing blood-brain barriers, I'm wondering if you can speak to the ALPL as a shuttle and what data we might expect to see this year to further characterize this platform.
The significance of ALPL or identifying the receptor is that the history in the field of AAV delivery is that you can find viruses that are very species-specific. We did not want to get a virus that only works in mouse or only works in non-human primates. Typically what we have done is to make sure that our capsids cross multiple species, but there is nothing like having identified the receptor. Then you know whether or not there is a human homologue. For ALPL, there is a human homologue. That has the risk to translatability as much as you possibly can before actually going into the clinic. Now that we have identified the receptor, we know that that receptor is leveraged to bring in a very large AAV particle, essentially a virus, into the brain.
The question is, can we leverage that receptor by making other kinds of ligands, conjugating them to protein therapeutics or oligonucleotides and get them into the brain as well? That is what we are working on.
Right. On the gene therapy side, the gene therapy field has suffered several setbacks recently. What makes Voyager different from the companies who have struggled?
I mean, I think that one of the issues was that the capsids were not optimally designed. I think delivery has hampered the field. If you do go to systemic delivery, we had to use very high doses, E14 VGs per kg range, which caused safety problems. By having neurotropic capsids, we hope to avoid the safety issues associated with localized delivery, such as intraparenchymal delivery. I remind you that Voyager was doing that years ago, intraparenchymally delivered AAV and stopped those programs. Going to IV delivery that crossed the BBB, and because they are so good at crossing, we hope to be able to use doses that are much lower than the E14 VGs per kg, at least an order of magnitude lower. That should be very helpful on the safety front.
I would say that with these localized deliveries, you get spotty delivery to certain parts of the brain. We want to optimize the efficacy as well. Many brain diseases affect large regions of the central nervous system, both the brain and spinal cord sometimes. The IV-delivered AAV promises to help on the efficacy side as well.
Right. How close are you to using your capsids in non-gene therapy modalities like oligonucleotide or enzyme delivery?
We're probably not going to use gene therapy to deliver oligonucleotides, but we want to be able to leverage the receptors that we discover through our TRACER platform to find AAVs across the blood-brain barrier, discover the receptors, and see if we can make ligands against those receptors, conjugate those ligands to protein or oligonucleotides, and deliver those AAV and get them into various tissues, into the brain, for example. This, of course, has been done very well with transferrin receptor, as you know. People like Denali have pioneered this. Other companies like Avidity and Dyne are working on muscle delivery. The TFR conjugation of these oligonucleotides and proteins seems to work. We think that our receptors may offer some differences that are going to be differentiated perhaps on distribution, on kinetics, and maybe on safety as well.
I think it's worth pursuing these other receptors to optimize brain delivery.
Right. Great. So then just on the Neurocrine partner programs, you have two INDs planned for 2025 with Neurocrine for Friedreich's ataxia and GBA1 Parkinson's. What's the latest on those programs?
Yeah, so it's a great partnership with Neurocrine. We have five programs that we're working closely with them. It's a great interaction, scientist to scientist. As far as we know, both programs are on track for IND filings that are expected this year, and that the clinical first-in-human studies are expected next year. I should remind you that Voyager gets up to $35 million in milestones for these products in this period. Very important to us.
Right. What biomarker clinical endpoints might be used to support early proof of concept, particularly for FXN?
I'd highlight really for both programs, the clinical development is really owned by Neurocrine. I can comment generally on the set of biomarkers for both programs. For frataxin, it's really going to be the key biomarker. I'd highlight that there have been some discussions with the FDA in the context of other programs where they've endorsed using frataxin as a biomarker for accelerated approval. I think measurement of frataxin is going to be key, particularly in the CNS and this context of a neurotropic capsid. I also think for GBA, there are a series of biomarkers you could consider using as well that will be quite important. Really, both programs fit into that concept of development programs that have a path to biomarker-based POC quite quickly.
Right. With 11 partner programs and up to $7.4 billion in potential milestones, how are you balancing internal innovation and external monetization?
We're always looking for business, for new partnerships, and expanding partnerships that already exist. This partnership has brought in a lot of our partnerships that we've already made have raised about $500 million in non-diluted revenue. The partnerships, as I said, the scientist-to-scientist interactions have been tremendous. We also intend to retain some wholly owned programs that we can advance in a very capital-efficient manner. We've built a world-class clinical development team under Toby, so we can do so.
Right. So what can we expect in terms of new partnership activity in the second half of 2025 and 2026?
As I said, we're always looking to talk to anybody about anything. I would just comment that we have two platforms now. One, the AAV gene therapy capsid platform. We have an emerging platform, the non-viral delivery leveraging these receptors. We're open to talking to partners about anything, either capsid or other licensed businesses, or even asset partnerships as we've done with both Neurocrine and Novartis.
Right. You've disclosed royalty terms for some assets, including SMA. What's the economic value of your partnered pipeline, and what milestones are expected next?
Let me take that one. This is a good question, but it's a very painful question because the real answer is it's massive, the value of those. As you look at our current market cap, it doesn't reflect that. Why would I say it's massive? There are 11 partnered programs. With those partnered programs, there's $7.4 billion in potential milestones. Of those, $2.6 billion are development. It's not a complete buy box. Also in there, there are high-value opportunities. Think about GBA for PD, SMA, Huntington's disease. These are high-value targets that we get significant royalties. I won't put a number on it, but I'll just say it's definitely multiples of our current market cap if some fundamental investor sat down and tried to value this out. Of course, in this market, it's difficult to get a deepened fundamental investor to do that.
Right. With $295 million in cash and runway into mid-2027, how are you prioritizing spend across the antibody, gene therapy, and platform initiatives?
Yeah, and the first comment I'll make on that, the $295 million gets us into mid-2027. That is enough to execute on Al's visions for the next couple of years, but it doesn't include our milestone payments. Those are on top of it. The milestone payments are on top of that runway guidance. In terms of how we're looking to prioritize, we don't actually—what I would say is we like all our babies, and we like the gene therapy that Al talked about. The shuttle is a very high priority for us internally. That doesn't mean it's a lot of spend. We just see there's a lot of opportunity there as we continue to execute on Al's multi-modality vision.
Al mentioned already that there's $35 million in milestones that we've guided to externally for the GBA and FA programs that we expect in the near term.
Right. Finally, what do you think the street is still missing about Voyager's story, and what are the key catalysts investors should be focused on in the next six to 12 months?
Yeah, so I think what they miss is we're not a gene therapy company. We're a multi-modality company, and that's with Al's vision from the beginning. If you want to invest in tau, you should put your chips on Voyager because we have the antibody program, we have the gene therapy program. In terms of the readouts, near term, we have the shuttle program that we expect to have some data again transferred on this year. Next year, we'll have our tau antibody data. That's pretty interesting data that's going to, with the tau PET data that Toby described. Also this year, Neurocrine is going to file a couple of INDs for our partnered programs. That isn't too far off. When I started at the company a few years ago, we were talking about data a couple of years in the future.
Basically, the future is now. It's in the next 12 months, we're going to have these transformative readouts. So it's a very exciting time to be here at Voyager.
Right. Terrific. Thank you so much. It's always a pleasure to catch up with you all on the team and to see how this incredible pipeline is advancing. Thank you to Al, Nate, and Toby, and thank you to Voyager for attending the conference. Thank you for all of our attendees for being with us. Have a great rest of your day and a great rest of your conference.
Thank you, Patrick.