Voyager Therapeutics, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Thanks for having me, Yan.

Sure. At the very beginning of the year, we put out a little shareholder letter that said there's three major things going on this year. One was related to tau. In fact, I called it the year of tau. That was in part because there's a lot of data coming from multiple companies on tau. We've seen that so far already. BIIB080, the tau silencing ASO from Biogen. Novartis had some data on PSP with a tau silencing ASO as well. We ourselves are about to have data from our multiple ascending dose study with an antibody directed at the C terminal of tau. This is called VY-7523, and we expect to see data in Q4 of this year, tau PET imaging data. In addition to that, we have a second program in tau, which is a gene therapy tau silencing approach where we're vectorizing an siRNA.

Very similar in terms of mechanism of action to BIIB080 and to the tau silencing ASO that Novartis has. That is why I call those two programs out, except that what we are doing is we are using AAV to express a vectorized siRNA to silence tau throughout the central nervous system. That is tau. The second piece is capsid POC. After many years, approximately 5 years of work, we have discovered these blood-brain barrier penetrant capsids that can get into the brain after IV delivery, get broad distribution throughout the central nervous system. We are entering the clinic, so this is the first test in humans now. We have two programs that are testing these novel capsids in humans. One is the tau silencing gene therapy program that I already mentioned, that we call VY1706. We have announced that we have FDA clearance and Canadian regulatory clearance.

We are activating sites as we speak. We expect to enroll the first patients this year, and we have said that we will expect to share acute safety data in Q1 of next year. Also in the second half of next year, we expect to share data that says that we are expressing the gene of interest, in this case, the tau silencing siRNA, in the second half of next year. That is the capsid POC. I should also say that our partners at Neurocrine have said that they are entering the clinic with also a blood-brain barrier penetrant capsid derived from our platform for Friedreich's ataxia. They are entering the clinic this year, and they said they expect to share data on that program next year. Two different programs that should provide proof of concept that our novel capsids work in humans.

The third thing, and the final thing, is we said that we would be showing more data on the NeuroShuttle platform. This is not AAV gene therapy, but it is basically leveraging the receptors that we discovered from our novel capsids. We reasoned that if these capsids get into the brain through the blood-brain barrier, they must be leveraging receptors to get there. We have discovered a handful of these receptors. The first one we have talked about publicly, it is ALPL. Much the same way that companies are leveraging transferrin receptor and CD98, we have these other receptors that we are leveraging as a shuttle for all sorts of modalities, antibodies, enzymes, peptides, oligonucleotides. We have said that we are going to share data. In fact, we have a plan now.

We have an abstract accepted for a meeting in December, where we are going to show a lot of animal pharmacology data, as well as with ALPL, the first of these receptors, as well as some of the safety data associated with ALPL shuttles. That is a high level overview of the three major, I would say, catalysts for Voyager.

Yeah. First I want to congratulate my former colleagues at Biogen for executing on that, on BIIB080, and for showing the results and telling us. We learned a lot by listening to what they shared with us at the scientific meetings this year, as well as their publications on the earlier phase trial. But the way I look at it, at a high level, I think it does validate tau as a target for Alzheimer's disease. I think the data on the cognitive measures, such as ADAS-Cog with BIIB080, were unprecedented in terms of efficacy, 50% roughly, 40-45%, 50% relative to placebo. Also on Mini-Mental State Examination, again, unprecedented levels of efficacy. On CDR-Sum of Boxes, it was sort of in the same range as the anti-amyloids, in the 20-ish percent range, 25% maybe.

Curiously, not so much of an effect on activities of daily living, which the anti-amyloid antibodies actually have no problem showing effects on ADLs, but for some reason, the tau-silencing BIIB080 did not. There were some questions that came out of that study as well, like why is there what seems like an inverted dose response curve? Biogen themselves say that they are moving into phase III with the lowest dose, which they think is in the sweet spot, if you will. It is hard to understand fully why the dose response was apparently inverted.