Good morning and welcome to Voyager Therapeutics First Quarter 2023 Conference Call. All participants are now in listen-only mode. There will be a question-and-answer session at the end of the call. Please be advised this call is being recorded at the Company's request. A replay of today’s call will be available on the Investor section of the Company’s website approximately 2 hours after completion of this call. I would now like to turn the call over to Pete Pfreundschuh, Chief Financial Officer. Please go ahead.

Thank you and good morning. Joining me on today's call are Dr. Al Sandrock, our CEO; Dr. Todd Carter, our Chief Scientific Officer. We issued our Q1 2023 financial results press release this morning. The press release and 10-K are available on our website. We plan to provide a brief summary of key highlights from the quarter and reserve the majority of time for your Q&A. In a moment, I will turn the call over to Al. Before I do this, I want to remind everyone that during this call, Voyager representatives may make forward-looking statements, as noted on Slide 2 of today's deck. These forward-looking statements include future expectations, plans, and prospects. All forward-looking statements are inherently uncertain and are subject to risks and uncertainties that may cause actual results to differ materially from those indicated by these forward-looking statements. You are encouraged to review and understand various material risks and uncertainties facing the Company as described in the Company's annual report on Form 10-K filed with the SEC. As in the filing of today's quarterly report on Form 10-Q, there have been no material changes to the risk factors described in our annual report. All SEC filings are available on the Company's website. Now, it is my pleasure to turn the call over to Al.

Thank you, Pete, and good morning, everyone. Please turn to Slide 3. I'd like to take a moment to recognize the incredible innovation happening right now in neurotherapeutics and in gene therapy. We believe we are witnessing a renaissance in neurotherapeutics. Just this year, the second disease-modifying therapy for Alzheimer's disease received accelerated approval and the first drug was approved for Friedreich's ataxia. We have seen breakthroughs in treating negative symptoms of schizophrenia, something for which there are no approved therapies. Just two weeks ago, the FDA granted accelerated approval to an antisense oligonucleotide for SOD1, amyotrophic lateral sclerosis. Importantly, the FDA based the approval on the finding that treatment-driven reductions in neurofilaments are reasonably likely to predict clinical benefit in SOD1 ALS patients, establishing a precedent for a biomarker-based path to accelerated approval. I hope this will drive further new treatments for patients suffering from this devastating disease. At the same time, the gene therapy field is coming of age. We have recently seen the FDA approval of the first gene therapy for hemophilia B. Gene therapies offering important potential advances in treating Duchenne muscular dystrophy and hemophilia A are approaching PDUFA dates. And through that, we may see the accelerated approval path utilized for gene therapy. Importantly, long-term data on Zolgensma, one of the first gene therapies approved recently, shows durability of effect after 7.5 years, which physicians have called transformational. Voyager sits at the intersection of neurotherapeutics and gene therapy, and we believe we are uniquely positioned to leverage the advancements in both fields. To date, the delivery of gene therapies into the central nervous system has proven challenging; approaches to inject these therapies into the brain parenchyma or various CSF spaces have not been very successful. Voyager TRACER discovery platform is the foundation of our approach to solving this delivery challenge. Voyager scientists have engineered multiple capsid libraries, each with more than 20 novel variants of AAV9 and AAV5 capsids, to select those novel capsids that display significantly increased transduction in the central nervous system following intravenous delivery. We have leveraged these capsids to advance our own and our partners' CNS gene therapy programs, several of which are now advancing towards clinical trials. This is how Voyager is enabling the future of neurogenetic medicines, and from where I sit, it's an incredibly exciting place to be. Moving to Slide 4, I will briefly review our investment rationale. Our first pillar of value is our TRACER capsid discovery platform, which I just discussed. In the preclinical studies, our novel capsids delivered intravenously have demonstrated more than 100 times higher transgene expression in the brain compared to conventional AAV9 capsids. We have shown high levels of CNS gene expression at low doses, and we have demonstrated the ability to target specific cells, such as neurons and glial cells, while also targeting in the liver and dorsal root ganglion cells. We look forward to sharing more data on our capsids at ASGCT later this month. Our second pillar of value is our CNS pipeline. We are advancing four programs through late research and towards IND. Two of these programs are wholly-owned: our humanized anti-tau antibody for Alzheimer's disease and SOD1 gene therapy program for ALS. The other two, our GBA1 gene therapy program for Parkinson's disease and our frataxin gene therapy program for Friedreich's ataxia, are being co-developed with Neurocrine. Our third pillar of value is partnerships. We completed collaboration and license agreements with Pfizer and Novartis. We have executed strategic collaborations around our pipeline programs with Neurocrine, and we are exploring more such transactions. Turning to Slide 5, we continue to make progress advancing our CNS pipeline. I'll note a few recent highlights. During the first quarter, we selected a lead humanized anti-tau antibody candidate, VYTAL 01, for the treatment of Alzheimer's disease. In March, we presented new data at the AD/PD meeting highlighting the differentiating characteristics of this lead candidate. Last month, we received pre-IND written feedback from the FDA for VY-TAU01. Voyager continues to expect to initiate GLP toxicology studies this year to enable an IND filing in the first half of 2024. Another change this quarter was to the timeline for our SOD1 ALS gene therapy program. Voyager previously stated we expected to identify a lead development candidate for this program in the first half of this year. That has moved out to the second half of this year as we continue to evaluate data from this program to identify the optimal development candidate. We intend to provide updated guidance on the IND timeline once we select the development candidate. Given where we are today, we expect the IND to occur in mid-2025. Our frataxin gene therapy program for Friedreich's ataxia and our GBA1 gene therapy program for Parkinson's disease and other GBA1-mediated diseases both continue to advance in collaboration with Neurocrine. I'm pleased with the progress we are making here. Additionally, during the first quarter, we launched two new early-stage gene therapy programs combining vectorized siRNAs with our novel intravenous TRACER capsids. One combines two siRNAs to enable specific knockdown of mutant HCT and MSH3 for the treatment of Huntington's disease. The other uses siRNA to reduce TAU expression in the brain for the treatment of Alzheimer's disease. I'd like to now turn the call over to Pete Pfreundschuh to discuss our financial results for the quarter.

Thanks, Al. I will cover some key financial points on this call and refer you to our press release and 10-Q issued today for further details. Please turn to Slide 6. We announced Q1 2023 collaboration revenue of $150.5 million, composed of $69.5 million from the 2023 Neurocrine collaboration agreement for the GBA1 program, $79 million from the Novartis option exercises, and $2 million from the 2019 Neurocrine collaboration agreement activities. Our R&D expense was $18.6 million, an increase of $4.2 million as compared to Q1 2022, driven by increased headcount, increased program-related R&D spend, and milestone fees, offset by decreased facility costs. Our G&A expenses were $9 million for the first quarter of 2023 compared to $7.7 million for the same period in 2022. The increase in G&A expenses was primarily a result of increased compensation costs driven by headcount increases. As a result of strong revenues in Q1 2023, the Company had a net income of $124 million, resulting largely from our collaboration revenues as well as increases of $1.8 million in other income due primarily to increased interest revenue from cash and marketable securities. Regarding the balance sheet, Voyager reported $273.3 million in cash, cash equivalents, and marketable securities at the close of March 31, 2023. We also had a receivable at the close of Q1 2023 from Novartis's $25 million option payment received in April. Together, this resulted in pro forma cash, cash equivalents, and marketable securities totaling $298.3 million at the close of the quarter. Notably, deferred revenue increased by $18.7 million related primarily to the upfront payment from Neurocrine allocated to the three new discovery programs of $74.4 million, offset by the recognition of $54 million into revenue from the Novartis options exercise. The Company has a strong balance sheet enabled by our non-dilutive collaboration revenues. We expect our balance sheet plus expected reimbursements will be sufficient to meet our planned operating expenses and capital expenditures into 2025. I will now turn the call back over to Al.

Thank you, Pete. Turning to Slide 7. As you can see, Voyager has had a productive start to 2023. We began the year by securing a $175 million upfront payment in a strategic collaboration with Neurocrine Biosciences, followed by Novartis's OPT-in decision on capsids to two neurologic disease targets, triggering another $25 million payment. These transactions strengthened our balance sheet and enabled us to further advance our platform and pipeline. As discussed, we selected a development candidate for our anti-tau antibody program for Alzheimer's disease. We aim to select a development candidate for the ALS SOD1 program later this year, and we launched two new early-stage gene therapy programs for Huntington's disease and Alzheimer's disease. In addition, I'm thrilled to welcome George Scangos to our Board of Directors, as we announced in our press release this morning. George is one of the most accomplished executives in the entire biotech industry, having served as CEO of Vir, Biogen, and Exelixis. His vast experience building biotech companies that deliver highly innovative therapies to patients while creating value for shareholders will be invaluable to us as we strive to develop Voyager into a leader in neurogenetic medicine. Looking forward, we continue our work to break through the barriers constraining the fields of gene therapy and neurology. We will continue to share the exciting data we are generating at scientific conferences, including at ASGCT later this month. Importantly, our pipeline advancement is leading towards what we view as multiple opportunities for value creation. As we look towards 2024 and 2025, we anticipate the potential for multiple IND filings across our wholly-owned and collaborative and/or licensed programs. This translates into multiple opportunities to earn milestone payments and, even more importantly, as clinical trials begin, several shots on goal to establish human proof-of-concept for our novel capsids. Furthermore, there is potential to see early biomarker-based evidence of disease impact in some of these very difficult CNS indications. And of course, we continue to engage in active discussions with potential partners around our platform and pipeline. In summary, it's been a great start to 2023, and as always, it is all due to the incredible Voyager team. I look forward to continuing our momentum throughout the year. With that, we're happy to take any questions you may have.

Thank you. The first question is from Jay Olson of Oppenheimer. Your line is open.

Congrats on all the progress, and thank you for taking our questions. We're interested in the work you're doing on tau; you're advancing an anti-tau antibody and initiating a tau knockdown gene therapy program and could potentially have a vectorized anti-tau antibody. Can you just talk about how you'll optimize the development strategy and prioritize all of your different tau targeting modalities? And then eventually, do you think that anti-tau therapies can be monotherapy or do you think they are best to be combined with anti-beta therapies? And then finally, can you just talk about how you'll balance the trade-off of advancing your tau therapy independently versus seeking a partner? Thank you.

Thanks, Jay. Those are great questions. So, first of all, what we like about tau is that we believe it's a very important and well-validated target for Alzheimer's disease and, because of that, we're taking multiple approaches against this target. So, as you pointed out, we have an antibody against the C-terminal domain of tau. The development strategy there is to move forward with the passive antibody first and see whether we can get proof of concept. In other words, to see whether we can block the spread of tau by looking at tau PET scans. We think this is very feasible and we can do it with not that many patients over a one-year period. If we obtain proof of concept, then we have a couple of choices there. One is we can continue to proceed with the antibody to tau all the way through to approval and/or we can then initiate a vectorized anti-tau antibody program. So, that would be sort of the crossroads that we will see there. In addition, we have this vectorized tau knockdown, which we think is an additional shot on goal against a very important target. And this will be different in the sense that it doesn't rely on antibodies binding to extracellular tau. This approach is to decrease the expression of all forms of tau, intracellular and extracellular. We saw some preliminary evidence of that approach at the AD/PD meeting with the Biogen Ionis antisense against tau, where they were able to see effects on tau pathologic imaging. So, we think it's a very important target. We think having multiple approaches is helpful against this target. We think we can obtain proof-of-concept pretty rapidly in the clinic, taking advantage of tau PET imaging. The final question relates to whether or not we are going to partner. We are always talking to partners and we are always open to anything. We could go to proof-of-concept by ourselves; we have the capability to do that, and I believe we have the resources to do that. However, we are open to anything. Ultimately, I can't imagine that we could go all the way to commercialization for a disease as large as Alzheimer's disease. So, we will need to partner that program. The question is when? We have some choices there. Finally, your question about combination or monotherapy: I believe, look, I think we just started the era of disease-modifying therapies for Alzheimer's disease with the accelerated approval of two beta antibodies. As we all know, the efficacy is modest in the 25% to 30% range on the CDR scale. We'd love to get better treatment effects. One approach might be to combine with a tau-reducing approach, whether it's an antibody or a knockdown. I think that we are likely to test combination treatments, because I think once tau spreading starts to occur, you may need to address tau independently or in combination with the amyloid antibodies. I hope that answers all your questions, Jay.

That was perfect. Thank you so much for taking all those questions.

Thank you, one moment while we prepare for the next question. And our next question will be coming from Jack Allen. Again, please wait for your name to be called before you ask the question. Your line is open.

Sorry about that. I was on mute. Thank you so much for taking the questions and congratulations on all the progress. I wanted to stick with the tau theme as well, and I wanted to ask Al, I'm sure you are aware of the Eli Lilly results from their recent study where they measured tau and stratified patients by tau. I was wondering if you had any early thoughts on a specific population within the Alzheimer's disease group that you looked to enroll? Any comments you may have around the differential effects it seems like Eli Lilly saw in their higher versus intermediate tau cohorts?

Hi, Jack. That's a really interesting question. I look forward to seeing the data at a scientific conference. From what I gather, the people who had the higher tau burden when they started the treatment had less of a treatment effect, and I think that underscores what I was just saying; we may need to combine with the tau approach, the tau-targeted therapy. In terms of the population, with mild cognitive impairment, which is the earliest symptomatic phase of the disease, the disease is pretty far along in terms of molecular pathophysiology. Not only has amyloid been accumulating for up to 20 years and reached essentially a maximum burden in the brain, but tau has already started to progress in many of these patients. I think that even when you do the combination, you're going to need to go to an early stage patient, at least MCI, and maybe even earlier.

Got it, great. Thank you so much for that insight into that. I was also wondering if you had any comments on the competitive landscape as it relates to tau and many other programs are closely monitoring to see early proof of concept in the space?

Well, I think that there are a number of domain-targeted antibodies that are now approaching readouts from efficacy trials, to my understanding. So that will be very interesting. In our hands, we had multiple mid-domain antibodies that we could have humanized ourselves. In our hands, they weren't as consistently effective in the spreading assay and in the animal studies where we took human pathological tau, injected it into the animals and looked at the spread of pathological tau. So, we're very hopeful that our anti-tau antibodies remain differentiated. I think it'd be wonderful to see efficacy with the mid-domain antibodies; these Alzheimer's disease patients need something additional, I believe, in addition to the anti-amyloid therapies.

And just wanted to add that, from our studies, at least in our preclinical models, it's pretty clear that the epitope matters quite a bit. So, the mid-domain antibodies of our own that work in antibodies don't work, or C-terminal, as Al mentioned, gave us the most robust and strongest effect. I think that as we see these antibodies come through the clinic, it will be very informative for the whole field to learn, hopefully, what works and maybe what doesn't.

Thank you, one moment while we prepare for the next question. And our next question will be coming from Philip Nadeau of TD Cowen. Your line is open.

A couple from us keeping on the tau team. In terms of the tau antibody that you've chosen as a development candidate, how does that antibody compare to the one that produced the data at AIC 2022? Is it simply a humanized version of that prior antibody or are there any other changes?

Go ahead, Todd.

Sure. We have shown data on a number of antibodies. The data you're talking about at AIC included data from multiple panels of antibodies with different epitopes. The antibody we're taking forward is a humanized version of the lead antibody from that presentation.

It's a humanized version of the antibody that produced the 71% to 74% declines in that?

Yes.

And then second on the GLP tox, it sounds like you're going to complete the GLP tox and be able to file an IND within a year; that timeline is faster than average. How can you get that done so quickly? Is that based on feedback from the FDA or just prior experience?

It's both actually. There have been other humanized antibodies against pathologic proteins. The tricky part here is that the target for the antibodies is not expressed in wild-type animals, which is typically what's used in toxicity species. To look at on-targeted toxicity, you have to look at animal models where that is the only place that you have the pathological tau being expressed. Those models, the animals don't do well; they die prematurely because of this disease. You have to work within the limitations of that. We do have experience with humanized antibodies against pathological proteins in the brain. We've drawn on that experience, but also, we have FDA feedback. Our preclinical toxicology plan is based on both.

And then one last housekeeping question for Peter. Peter, the $25 million milestone that was received in April, is that all going to be booked in Q2 or is there going to be an amortized component?

We recognized recorded that the spin Q1, but cash is perfect. You should see that in the numbers.

Thank you, one moment while we prepare for the next question. And our next question will be coming from Yanan Zhu of Wells Fargo. Your line is open.

Hi, thanks for taking our questions. Perhaps the tau question and a solid one ALS question. So for tau, how would you think about the criteria for success once you get the tau antibody PET imaging data given the findings of the tau antisense, as you mentioned before? I'm guessing mainly if tau reduction on PET is less potent, then if there's still a reason that the antibody approach can be a reasonable modality to be further pursued. On TAU01, could you give more color on the delay for the nomination of the candidate? Is it more about payload or vector optimization or some other reasons? Thank you.

Those are great questions. I'll take the first one, and Todd will take the second one. On the tau, well, first of all, the antisense oligonucleotide is injected intrathecal, and our antibody is an intravenous drug that we're going to inject every four weeks. That's a pretty big difference right there in the mode of administration. We will, of course, compare to others that are showing data on tau. We do have a minimum product profile that takes into account our competition. We will move it forward if we have, first of all, to have a statistically significant reduction in the spread of tau. We'll compare to competitors and see if there's space for an additional treatment. Just keeping in mind the different modes of administration, the higher ease of use of an intravenous antibody, and the fact that I think there is room for more than one treatment. When I was a physician, I always liked having multiple options for my patients. Todd?

Yes. So, on Slide 1, as you know, I've pointed out, development candidate and therapy is the combination of a capsid and a payload, the transgene. We're continuing to work and evaluate the transgenes and our capsids. Our capsids continue to perform very well. I invite anybody on the call to check out the ASGCT presentations next week. We have a couple of presentations and posters on our novel capsids. We are seeing quite reproducible results and continued performance across the membrane barrier. What we're trying to do is identify the optimal payload with the optimal capsid to meet our candidate criteria. We hope to do that in the back half of this year.

Thank you and one moment while we prepare for the next question. And our next question will be coming from Laura Chico of Wedbush. Your line is open.

Good morning. Thanks very much for taking the question. I guess, Al, staying on this tau theme. I wanted to ask if with the upcoming reimbursement decision for the anti-amyloid antibodies, is there any learnings there that can inform or perhaps change your development strategy for tau? And then one for Pete, can you just remind us, it's obviously been a big year in terms of milestone coming in, any potential for remaining milestone payments in 2023? Thanks, guys.

Thanks, Laura. Yes, on the reimbursement question, that's a really important question and we have a lot to learn, I think, as the year goes on. I think, look, we have to be mindful of the total number of patients that are going to require treatment, and we don't want to do anything that will be unhelpful to society. We want to help patients and make sure they have access to the drug. There's a lot for all of us to learn in the coming years. You are pointing to the concept that if there is a combination treatment, that's two drugs that have to be reimbursed, and we must take that into account.

Yes, Laura, with regards to your second question. We don't provide a lot of forward-looking guidance with regards to future milestones. I know we have shared publicly the milestones relative to all of our partnerships and relationships in aggregate, with some breakdown. A lot of that's been redacted. I can say it this way: with regards to our existing relationships, there are some potential milestones that we could be getting in more of a near-term, I would say it that way. But again, we don't guide specifically with regards to those when we see, that's probably where we would leave it for now.

Thank you and one moment while we prepare for the next question. And our next question will be coming from Joon Lee of Truist Securities. Joon Lee, your line is open.

Thanks for taking our questions. For the Huntington's program, it's interesting that you are taking both a specific and non-specific approach with SNP and MSH targeting. Can you elaborate a little bit on your strategy here, and do you plan to include multiple siRNAs in a single construct to address multiple SNPs? And would you also combine a SNP, as well as MSH to a single construct?

Yes, I'll start and I'll ask Todd to finish the answer. I would say that in some ways, both are kind of an allele-specific approach because MSH3 targets the expansion, which only occurs off the mutant. The allele-specific mutant huntingtin target is an allele-specific approach. Both are preserving wild-type Huntington expression, which is the goal, because there’s concern that we need to preserve wild-type Huntington expression. I mean, I'll let Todd answer. But our aim is to combine both siRNAs into the same vector.

That's right, Al. We do plan on incorporating both siRNAs; the payloads for the siRNAs are relatively small, so it's not a problem to fit multiple in a single vector. We can do a bicistronic approach; we could evaluate them independently as well, so that's always an option we could choose to move forward with. We plan on going after MSH3 in a pan manner, which would affect the mutant allele specifically. Then the approach to the allele-specific Huntington's is a SNP-based approach to knock that down and then only target the mutant allele.

You're right that the SNP-based approach, we're not going to be able to treat every single Huntington's patient. We'll start with the most common alleles, and then ultimately, we may need to do a second allele-specific HTT program, and so forth.

I have a follow-up on the tau program. You have, as some people alluded to, multiple programs, multiple shots on goal. You have the approach to targeting extracellular species as well as intracellular species with siRNA. Is there one species in your view that is probably more important to address? So, I know you’ll probably say both, but which one has more evidence as a more dangerous or pathogenic form?

Well, I wish I knew the answer to that question. I think that's part of the complexity here; there are multiple forms, if you will, of tau in the extracellular space. It's pretty certain that targeting just intracellular tau probably doesn't work because multiple approaches have been tried. I don't have an answer, but maybe Todd does know what the pathologic species are.

No, I don't.

More along the lines of intracellular versus extracellular because your siRNA approach, the target, I believe, preferentially targets intracellular species?

Yes, well, that actually will target both. I mean, it'll target the synthesis of all forms of tau. If we decrease, we will definitely increase intracellular, which the antibody probably won't be able to do very much at all. But it will also eventually target extracellular tau too because that's the source of extracellular tau is intracellular tau.

Would you say that the siRNA approach would have a little bit higher project success, or that's still TBD?

Well, yes, but every approach is going to have its own benefit-risk profile and mode of administration issues and things. So, I think it's still too early to know for certain which approach is going to be optimal for patients. But I think it's such an important target that we wanted to go after it with multiple approaches.

The next question is coming from Sumant Kulkarni of Canaccord. Your line is open.

Thanks for taking my question and nice to see all the progress as the Company has worked here in exciting times to be targeting the specific conditions that you are. So, I have a question on your SOD1 ALS gene therapy program. Now that Tofersen is available, how do you expect the landscape to change with respect to clinical trials recruitment? And then in medicine running a specific preclinical model in combination with Tofersen?

Okay, I think I heard the first question. But I'll start, and then I'm not sure I heard the second one. First of all, it's wonderful that patients with a terrible disease have treatment options, so congratulations to Biogen and Ionis for getting that across the finish line. For us, we can take patients who are already on Tofersen and see if they require treatment for gene therapy and see if the requirement for Tofersen is decreased, perhaps to zero, but it could just be decreased. We can track neurofilament as a marker to know whether the treatment is adequate. Another approach would be to go to untreated patients; there may be parts of the world where it's hard to access Tofersen. A third approach would be to go very early, even before symptoms, to get rid of the toxic gain-of-function autosomal dominant mutation. Those are the three approaches we’re considering now. Time will tell which option is the best, but the fact that neurofilament is considered by regulators, at least the FDA, as a validated surrogate outcome measure only helps in terms of making development more feasible, I believe. And then I can discuss. You may have to repeat the second question because I'm not sure I heard it.

The second part of that was, is there any merit in running a specific preclinical model for your gene therapy in combination with Tofersen to optimize the product?

So, the question was whether we're doing preclinical studies. There are a couple of SOD1 transgenic mouse models, G93A, G37R, et cetera. We could add in vivo combination studies. I'm not certain that would be necessary before we did studies in patients. I think that we have a good blood-based biomarker that we can use to monitor patients regarding the amount of injury to motor neurons. Some of these animal models, they're not very predictive of what happens in the clinic. So, I worry about relying too much on these animal models.

The next question is from Jack Allen of Baird. Your line is open.

Thank you so much for taking the follow-up. I just wanted to reach out and see if you have any comments around the availability of non-human primates. I know earlier this year, there was a ban on the importation of these critical research assets. I wanted to gauge your awareness of this and any comments you have as it relates to your preclinical programs that you have ongoing?

Hi, Jack, it's Todd. It's a great question. I think the entire field is watching very carefully. We certainly are watching the availability of non-human primates quite closely. To date, we have not been adversely affected by non-human primate availability. We set up agreements with multiple vendors to make sure we have options in case an issue should arise. All I can say is that we’re doing our best to mitigate any risk and watching very closely.

Thank you. This concludes today's Q&A session. There are no more questions in the queue. I would like to turn the call back over to Dr. Al Sandrock for closing remarks.

Thank you, everyone, for joining us today and for the great questions. Feel free to follow up with us directly if you have any further questions. Thanks again.

Thank you everyone for joining today's conference call. This concludes today's event. You may all disconnect and everyone have a great rest of your day.