Voyager Therapeutics, Inc. (VYGR) Earnings Call Transcript & Summary

Good morning, and welcome to the 42nd Annual JPMorgan Healthcare Conference. My name is Dave Praharaj, and I'm part of the Healthcare Investment Banking team here at JPMorgan. Today, I have the pleasure of introducing our speaker, Dr. Al Sandrock, CEO of Voyager Therapeutics. In terms of 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 4 things: our pipeline, which consists of a wholly owned pipeline as well as some partner programs in neurogenetic medicines with at least 4 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 2E12 vg/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. And I'll also talk a bit about our potential. We do have programs now in antibody therapeutics as well as gene therapy. But we have the potential to expand within neurogenetic medicines. And 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 2 additional ones we've identified. These receptors basically explain how these capsids 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 subsequent public offering which extends our runway into 2027. 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, 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 2 programs, Huntington's disease and spinal muscular atrophy. They fully reimbursed 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 going to 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, Novartis receives worldwide rights to our Huntington's disease program, where we vectorized siRNAs to reduce the expression of mutant Huntington in an allele-specific way. And we also, in the same vector, reduce the expression of MSH3. In SMA, they have worldwide rights to our -- any of the 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 boxes. Well, I just talked about the Novartis 2 transaction. That builds on a partnership that was actually -- that's called NVS1 there. That was -- the first partnership was signed in March of 2022. So the context is important here because they've been doing experiments in their own labs with our capsids since March of 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. The Novartis partnerships, both of them build on the other partnerships, actually, one year ago, roughly this week, we announced a deal with Neurocrine on GBA1. GBA1, if you have homozygous deletions of GB1, you get Gaucher disease, heterozygous. So carriers of GBA1 have a high risk of Parkinson's disease. So that deal was signed as well as 3 undisclosed targets approximately a year ago. And that's on the heels of NBIX1 partnership that was signed several years ago around Friedreich's ataxia plus 2 targets. So that's a total of 7 programs that we're collaborating with Neurocrine on. Down below, you see Alexion. Alexion acquired the rare disease group or the rare disease portfolio from Pfizer. And so 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 wholly owned programs. So we have 4 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 3 gene therapy programs, the first of which is another vectorized siRNA. This one to knockdown the expression of SOD1 responsible for an autosomal dominant form of ALS. And in addition, we have 2 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 4 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 -- but we're very confident in our partners. This is not about -- just about the money. 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. And we've done so in the past and we will -- and you can be sure that we plan to share data this year because we continue to innovate on the gene therapy front. And 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 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 and which is the little yellow dot at the origin. So AAV9 was, at one point, the leading neurotrophic capsid. In fact, Zolgensma is an AAV9 gene therapy. So what we're plotting now is fold improvement over AAV9 with IV delivery in mouse on the Y-axis and a nonhuman 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 a very high bar for our capsids. 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 C-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 mutation, we made over 100 million of them. We found a few that get across the blood-brain barrier. The question was, well, molecular -- 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 called, 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 macro molecules to those ligands. So proteins such as enzymes and monoclonal antibodies were conjugating to ligands against Receptor X as well as nucleic acids. And wouldn't it be great if we could deliver those macro molecules across the BBB without the use of AAV. Be it 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, there's data that's coming in 2026 that I want to 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 Ia Single Ascending Dose study this year. And then next year, we've initiated a Phase Ib 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 expect 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 time frame. So our own wholly-owned SOD1 ALS program, we expect to enter the clinic in mid-2025 and Neurocrine has already said that they expect to initiate 2 gene therapy programs in the same year. So 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 started doses that have like -- that have at least a good likelihood working in humans. Otherwise, it's not ethical to use gene therapy in patients. So if we start those studies in 2025, by 2026, we should have some data, at lease 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 that's why we did the additional $100 million raise. Now in addition to that, we always are looking to add to our pipeline. We have a number of programs that are kind of sitting in the queue, 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?

Yes. So as I said, our scientists have been collaborating for about a year and 9 months. And in that first deal, they've 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 it was in that setting that they decided that they wanted to do additional program work with us. SMA and HD was not available to them in the first deal because we were already working on those programs. So it was an incumbent program, if you will. And so that's what led to the second deal.

That was a great talk, Al. I have a very basic question. This is a [indiscernible].

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 conference right now. Can you talk a little bit, as I say, this is a basic question, what's the principle here, how long do the antibodies circulate? Can you just explain more about that novel platform?

Yes. So this is a program that's been in existence at Voyager for a number of years. There was originally a collaboration with AbbVie around vectorizing antibodies, I believe for tau, is that right, Todd?

Yes.

And what you basically do is express the heavy chain and light chain even though AAV has certain payload limits, and the 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. How long? Hopefully, for many, many years, but we have data in our own labs where the expression can go on for years in nonhuman primates, if I'm not mistaken, Todd, is that true?

With different payloads, yes.