Good morning, and welcome to the 42nd annual JP Morgan Healthcare Conference. My name is Dave Praharaj, and I'm part of the healthcare investment banking team here at JP Morgan. Today, I have the pleasure of introducing our speaker, Dr. Al Sandrock, CEO of Voyager Therapeutics. In terms of the logistics, please reserve any questions for after the presentation, as we will have time. With that, take it away, Al.
Thank you very much. Thank you very much. Good morning, ladies and gentlemen, and it's my pleasure to tell you about Voyager and how we're defining neurogenetic medicines. What I'll be telling you about today is basically four things: our pipeline, which consists of a wholly owned pipeline, as well as some partnered programs in neurogenetic medicines, with at least four IND filings this year and next year, potentially generating clinical data in 2025 and 2026. I'll be telling you about our platform, focus on our TRACER-derived capsids. We believe this is a leading platform, the leading platform for CNS gene therapy, with multiple capsid families that cross multiple species, with very high levels of transduction of cells in the central nervous system at low doses.
For example, at last year's ASGCT, we presented data in marmosets using doses in 2 × 10^12 vgs per kg, producing greater than 50% transduction of cells. I'll also be telling you about our partnerships, for which we're very grateful. They bring strong cash position with runway into 2027, and that's not including potential milestones down the line, which can bring in up to $8.2 billion. I'll also talk a bit about our potential. You know, we do have programs now in antibody therapeutics as well as gene therapy, but we have the potential to expand within neurogenetic medicines.
Right now, we're doing experiments, thinking about or discussing and actually doing experiments in animals where we plan to leverage this receptor we discovered, one of the receptors, which will be called Receptor X, as well as two additional ones we've identified. These receptors basically explain how these capsids cross it, cross the blood-brain barrier into the brain, and we're doing experiments on that as well. You may have heard, last week, we just announced a transaction with Novartis, as well as a subsequent public offering, which extends our runway into 2027. You know, Novartis is a world-leading partner.
They know more about gene therapy, I believe, than anybody else, certainly about the development, manufacturing, and commercialization, as they have a very successful product called Zolgensma, that really has, you know, what I consider transformational effects on babies with SMA. For that, in that partnership, we received $100 million upfront, which includes $20 million of equity investment. It funds two programs, Huntington's disease and spinal muscular atrophy. They fully reimburse us for the Huntington's program up until the IND, then they take the ball from there and go to commercialization, hopefully. On SMA, they take over right away, as they have significant payload capabilities, but they're gonna take one of our capsids into research and development.
significant potential future value in that, we have up to $1.2 billion in potential milestones, with high single-digit to low double-digit tiered royalties on annual global sales of the collaboration products. So in exchange for that, you know, Novartis receives worldwide rights to our Huntington's disease program, where we vectorize siRNAs to reduce the expression of mutant huntingtin in an allele-specific way, and we also, in the same vector, reduce the expression of MSH3. In SMA, they have worldwide rights to any of our TRACER capsids they choose to work with. So a very nice deal for us, and I hope Novartis feels the same way. This slide talks about all the other partners.
In the box is what I just talked about, the Novartis-2 , transaction. That builds on a partnership that was actually that's called NVS-1 there. That was signed. The first partnership was signed in March 2022. So the context is important here because, you know, they've been doing experiments in their own labs with our capsids since March 2022, and against that backdrop, they decided to do additional partnering programs with us. I think that speaks highly for the fact that our science is appreciated and reproducible in their own labs. You know, the Novartis partnerships, both of them, build on the other partnerships. We actually, one year ago, roughly this week, we announced a deal with Neurocrine on GBA1.
GBA1, if you have homozygous deletions of GBA1, you get Gaucher's disease. Heterozygous, so carriers of GBA1, have a high risk of Parkinson's disease. So, so that deal was signed, as well as three undisclosed targets, approximately a year ago. And, that's on the heels of an MBX-1 partnership that was signed several years ago around Friedreich's ataxia, plus two targets. So that's a total of seven programs that we're collaborating with Neurocrine on. Down below, you see Alexion. Alexion acquired the rare disease group, or a rare disease portfolio from Pfizer. And so they originally that deal was done with Pfizer, but now it's in Alexion's hands, and that's for one rare disease neurologic target, and last year, we signed a deal with Sangamo for prion disease. So here's what our portfolio then looks like.
At the top are our wholly owned programs. So we have four programs. The first is actually not a gene therapy. It's a humanized monoclonal antibody against the C-terminal of TAU, VY-TAU01, and we plan to file an IND in the next few months. So we'll return to being a clinical stage company shortly. And I'll talk more about that program and what we expect to see downstream in a minute. In addition to that program, we have three gene therapy programs, the first of which is another vectorized siRNA, this one to knock down expression of SOD1, responsible for an autosomal dominant form of ALS. And in addition, we have two Alzheimer's disease program. So tau is such an important target, that we also have a vectorized siRNA knockdown program for tau.
And then we have a vectorized antibody against A beta or an anti-amyloid program as well. So those are our four wholly owned programs, in addition to the Neurocrine partnered programs and Novartis partnered programs, as well as capsid licenses. That's a total of 17 programs, which is quite a lot. Fortunately, we don't have to pay for all of them, but hopefully, b ut, you know, we're very confident in our partners. You know, this is not just about the money, and we hope that our capsids will be used by our partners and by our own team to make some meaningful therapies for patients. We plan to continue to share our data at scientific meetings.
We've done so in the past, and we will and you can be sure that we plan to share data this year, 'cause we continue to innovate on the gene therapy front. And, you know, our partners have noticed, including Bob Smith at Pfizer and Jude Onyia, the CSO at Neurocrine, who is also on our board. So our platform. So what, why do these companies want to work with Voyager? Well, it's because we've improved on the capsids, and we believe this was a pretty critical issue to solve in order to enable gene therapy for the central nervous system.
The graph on the right plots some of the capsids we've discovered, and what we're plotting here is the fold improvement over AAV9, which is that little yellow dot at the origin. So AAV9 was, at one point, the leading neurotropic capsid. In fact, Zolgensma is an AAV9, a gene therapy. So what we're plotting now is fold improvement over AAV9 with IV delivery in mouse on the Y-axis and a non-human primate brain on the X-axis. And what we're showing is that the first generation of capsids were a great improvement, but the second generation of capsids is even better. We're now in the 100-fold improvement range.
So we think this is important because we can lower the dose, so for safety reasons, but also, we hope to achieve greater levels of CNS cell transduction so that we can achieve better efficacy as well across the brain and spinal cord broadly. So, we have very high bar for our capsids. You know, in addition to the tropism and the lower dose, we want to see cross-species validation. There's a history in this field of having very species-specific capsids, and we want to avoid that. We want our capsids to work in humans, so we insist on cross-species validation. And the other thing we've done is to look for the receptor, which is not an easy thing. So since we have these, we make these essentially random mutations, we made over 100 million of them.
We found a few that get across the blood-brain barrier. The question was: well, in molecular terms, how does that happen? What is the receptor by which these capsids get into the brain? And we were lucky enough to identify several. The first one, which we call receptor X, we know the most about. First, we know that it's present in humans, so that greatly increases the likelihood that our capsids will work in humans. But also, as I said earlier, what we're doing is making ligands against receptor X, and we're conjugating various macromolecules to those ligands. So proteins, such as enzymes and monoclonal antibodies, we're conjugating to the ligands against receptor X, as well as nucleic acids. And wouldn't it be great if we could deliver those macromolecules across the BBB without the use of AAV?
Be yet another way to deliver medicines into the central nervous system. The raise we did last week, right after the heels of getting $100 million upfront in cash from Novartis, was important for us, because it extends our runway into 2027. And so what does that enable? Well, first of all, you know, there's data that's coming in 2026 that I wanna share with you, that it will hopefully get us to. So first, as I mentioned earlier, we plan to file an IND with our lead program, VY-TAU01, in a few months. That should let us proceed to a phase 1a single ascending dose study this year.
And then next year, we plan to initiate a phase 1b trial, where we plan to employ tau PET imaging to hopefully obtain a proof of concept. And what we're trying to do is to see whether the antibody blocks the spread of tau in humans with Alzheimer's disease. And we expected the key readout from that to occur in H2 of 2026, as shown here. So that's why it was important to extend the runway into 2027. In addition to that program, we have several gene therapy programs entering. We expect to enter into the clinic in the 2025 timeframe. So our own wholly-owned SOD1 ALS program, that we expect to enter the clinic in mid-2025, and Neurocrine has already said that they expect to initiate two gene therapy programs in the same year.
So, you know, in gene therapy, you start right off in patients. It's unethical to treat normal healthy volunteers with gene therapy, so you start right away in patients, and you also start at doses that have a likely... that have a, at least a, a good likelihood of working in humans. Otherwise, it's not ethical to use gene therapy in patients. So, you know, if we start those studies in 2025, by 2026, we should have some data, at least safety data, if not biomarker and other kinds of data, that establish that our genes are being expressed in the central nervous system. So that's what we hope, and, and that's why we did the additional $100 million raise.
Now, in addition to that, you know, we always are looking to add to our pipeline. We have a number of programs that are kind of sitting in a queue, and, and we'd love to initiate. And we also always are talking to partners, potential partners. And hopefully there'll be more to announce there as well. So with that, I'll thank you and take questions.
Thank you, Al. I will kick off the questions. So, Voyager started off the year with some big news, like you mentioned, the $100 million upfront deal with Novartis. Can you just tell us a little bit more about, like, how it came together?
Yeah. So as I said, you know, our scientists have been collaborating for about 1one year and nine months, and in that first deal, they'd been doing experiments in their own labs with our capsids. But as part of that deal, we're obligated to share with them updates on our newer capsids, our second gen capsids. And so that has been an ongoing thing, a great collaboration, scientist to scientist. I get to join some of those, so I enjoy them. And, and it was in that setting that they decided that they wanted to do additional program work with us. You know, SMA and HD was not available to them, in the, in the first deal because we were already working on those programs. So it was an encumbered program, if you will.
So that's what led to the second deal.
Thank you.
Hi. That was a great talk, Al, and, I have a very basic question. This is Ilana Rhein.
Yeah.
Uh, and
I can see you, even though there's a bright light right behind you.
I'm hiding. Vectorized antibodies is not something that's being discussed in all the rooms of the
Mm
conference right now. Can you talk a little bit, as I said, this is a basic question: What's the principle here? How long do the antibodies circulate? Can you just explain more about that
Yeah
novel platform? Thank you.
Yeah. So, this is a program that's been in existence at Voyager for a number of years. That was originally a collaboration with AbbVie around vectorizing antibodies, I believe, for tau. Is that right, Todd? Yeah. And, what you basically do is express the heavy chain and light chain. You know, even though AAV has certain payload limits, its payload limits don't allow for the full antibody, both heavy and light chain, to be expressed. And we can express them in glial cells. And we have shown, actually, we have shared data in a scientific meeting where we can actually express the antibody for long periods of time. You know, how long? Hopefully for many, many years.
But we have data in our own labs where the expression can go on for years in non-human primates, if I'm not mistaken. Todd, is that true?
With different payloads, yes.
Yeah. So that's the principle, Ilana.
There's a question over there.
Thank you, Al, for the presentation. You just talked about this AAV payload limitations. Do you have ideas or plans also to deliver larger genes?
Well, there are ways that people have thought about how you deliver pieces of genes and put and combine them, essentially. But, you know, in our hands, from almost all the targets that we're interested in, we actually can address them with AAV. Not the very large, we can't put the whole dystrophin gene in there, obviously. But for most of the diseases we're interested in the central nervous system, we actually have an approach. And I think it's important to point out that in addition to vectorizing antibodies, we can vectorize siRNAs to knock down expression. We can replace enzymes. GBA is gonna be an enzyme replacement. And SMA is basically replacing SMN protein.
We're not working on enhancements of the payload ourselves, as where larger payloads can be delivered, but I know several other groups are.
So you mentioned Voyager completed, you know, the $100 million public offering last week, on the back of the Novartis deal. What was kind of the rationale there?
Yeah. So I think I've already stated that, but it really was to get to some critical data readouts in the-- that we're expecting to happen in the second half of 2026. The key one being the VY-TAU01 tau PET imaging data. But in addition, you know, we'll have more than six months of follow-up, potentially even a year of follow-up, on three separate gene therapy programs. Certainly, we'll have some early safety data. We may even have some early biomarker data that show that we're getting gene expression in the adequate amounts. And we hope to be doing that y ou know, we would consider a failure if we have to go to doses as high as E14 VGs per kg.
We hope to be able to show that at lower doses, perhaps through E13 or less VGs per kg, that we can not only safely give our gene therapies, but get enough into the brain to give us adequate gene expression. I think that would be a very important piece of information for us to get to. And so we wanted to ensure a runway to get to those inflection points, if you will.
I guess to follow up on that, any particular one that you're most excited about in terms of inflection points?
Well, you know, I'm excited about everything, otherwise it wouldn't be there. But, you know, look, I mean, I think tau is a very important target. And, you know, we just are at the dawn of therapeutics, disease-modifying therapies for Alzheimer's disease. And I think tau is the next target. The first generation of drugs target beta amyloid. It's very important to note that with the beta amyloid antibodies, the only ones that work are directed against the N-terminal. In the case of A beta, epitope matters quite a lot. With tau, we don't actually know what the right epitope is, we meaning the world. We know that the N-terminal ones don't work. That, I think, is pretty certain given some of the clinical trial data.
But where in the other parts of the tau protein we need to target, we don't know. We've chosen the C-terminal domain, because in our hands, it blocks the spread of tau the best in animals. And so we've taken that forward. But, you know, there are other programs directed against the MTBR, the microtubule binding region, as well as other mid domain regions, and there's a couple competing with us on the C-terminal as well. But, you know, the great thing here is that we can get efficient proof of concept by doing tau PET imaging. And that's how the whole anti-A beta field started. You'll remember that the first piece of data that suggested that we were on the right track was amyloid PET imaging data, back in 2016 or so.
So, I think the same thing could be happening with tau. So I'm excited about tau, but, you know, being able to treat ALS with a one-time IV dose is also pretty cool. And, look, ALS is one of the most horrible diseases that I've ever dealt with as a physician. And, boy, it'd be nice to be able to help patients with a one-time IV gene therapy that gets into the brain and spinal cord. So I'm excited. As you know, I didn't really answer your question because I'm excited about all these things.
Thank you for the presentation. My question was on the 100, a 100 times, like, fold improvement over the AAV9. I was wondering what were the metrics that went into measuring that, and if that included potential off-target effects?
Yeah. So very, very nice question. So we look at DNA, so vector genomes per cell, we look at messenger RNA, and we look at protein. So when we look at the expression of. When we look at whether these capsids can deliver, we don't just stop at showing that the DNA gets in. We wanna be sure that the episomes are produced productively, and that they can actually make messenger RNA and protein as well. And we also look at off-target effects, as you pointed out. We want to de-target the liver. So, fortunately, many of these capsids that are incredibly potent at getting into the central nervous system actually de-target the liver quite substantially. And as you know, liver, the liver is a major source of toxicity with systemic gene therapy.
And so we're very happy to, we were very happy to see that our capsids de-target the liver. Many of them also de-target the dorsal root ganglion neurons, another cell that has been implicated as a potential toxicity, although we haven't really seen clinical manifestations of that. Pre-clinically, one sees dorsal root ganglion neuron toxicity, so we also look for capsids that can de-target that cell as well.
Any other questions? Well, with that, with that, we'll give everyone a, the gift of time. Thank you.
Thank you.