Good morning and welcome to Voyager Therapeutics Second Quarter 2023 Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that 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 two 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 the call today are Dr. Al Sandrock, our Chief Executive Officer; Dr. Todd Carter, our Chief Scientific Officer. We issued our Q2 2023 financial results press release this morning. The press release and the 10-Q are available on our website. 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 in Slide 2 of today's deck. These forward-looking statements include future expectations, plans and prospects. All forward-looking statements are inherently uncertain and 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 the various material risks and uncertainties facing the company as described in the company's most recent annual report on Form 10-K filed with the SEC. As of 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 start by recognizing the incredible innovation happening right now in neurotherapeutics and in gene therapy. I talked about this on our last call. And since then, we continue to see tremendous progress. On the neurotherapeutics front, just last month, lecanemab received full FDA approval for Alzheimer's disease as well as Medicare coverage. This follows other recent FDA approvals in the neurotherapeutics space, including approvals of medicines for Friedreich's ataxia and amyotrophic lateral sclerosis. The gene therapy field also continues to advance with recent FDA approvals of the first gene therapies for Duchenne muscular dystrophy and hemophilia A. Voyager sits at the intersection of neurotherapeutics and gene therapy. We believe we are uniquely positioned to leverage the advancements in both fields, and importantly to combine them. To date, the delivery of gene therapies into the central nervous system, or CNS, has proven challenging. Approaches to inject these therapies into the brain parenchyma or various cerebrospinal fluid spaces generally have not been successful and continue to result in setbacks for other companies. Voyager recognized this back in 2021. That's why we pivoted to intravenous delivery, leveraging the vasculature to penetrate the CNS, something we have enabled through our innovative capsid design. Moving to Slide 4, I will briefly review our investment rationale, platform, pipeline, partnerships and potential. First, the platform. Voyager uses our TRACER capsid discovery platform to generate multiple families of novel capsids with robust CNS tropism following IV delivery. We have presented data demonstrating strong transduction to multiple areas within the brain and activity across multiple species. Our most recent data at the American Society for Gene and Cell Therapy, or ASGCT, 2023 Conference showed greater than 50% transduction in multiple brain areas at the relatively low dose of 2E12 VG per kilogram in marmosets. Second, our pipeline. We are advancing four CNS programs through late stage research and towards IND filings, including our wholly owned anti-tau antibody for Alzheimer's disease and SOD1 gene therapy program for ALS. We currently have three wholly owned assets targeting Alzheimer's disease, including the new early research initiative just announced today to advance a vectorized anti-Aβ antibody. We'll talk more about this in a minute. Third, partnerships. Voyager has generated more than $200 million this year alone in non-dilutive partnering revenue. In Q2, we executed a license agreement with Sangamo around prion disease, bringing our total number of partner programs to 11. These programs provide opportunities for additional milestone and/or royalty revenue to Voyager as well as opportunities to generate data with our capsids, and most importantly, to help patients. Finally, potential; specifically the potential to expand from gene therapy into other approaches of neurogenetic medicine. As those of you who attended our standing-room-only talk at ASGCT know, we are making good progress in our receptor program. After identifying a receptor for one of our capsid families, we have now also identified a ligand for this receptor, which has many of the characteristics required for transport of macromolecules across the blood brain barrier, or BBB. We are exploring the potential to leverage the receptor to shuttle non-viral genetic medicines across the BBB. We have also preliminarily identified two receptors for additional families of our TRACER capsids and we are conducting confirmatory research to further validate these discoveries. While this program is early, I'm increasingly excited about the potential here to expand the reach of our technology into other approaches of neurogenetic medicine. Moving to Slide 5. As you can see, Voyager is advancing quite a robust pipeline. However, we are doing so efficiently. The four programs depicted in blue at the bottom of the slide are funded and executed by partners. They do not require a significant investment of time or money from Voyager. Moving up the slide, the seven programs depicted in yellow represent our collaborative programs with Neurocrine. For these programs, Voyager's fully reimbursed for our collaborative research. The six programs depicted in orange at the top of the slide represent our wholly owned pipeline. This is where I will focus today. Turning to Slide 6. You can see that our wholly owned pipeline now includes three programs for Alzheimer's disease. Our lead program is our humanized anti-tau antibody, which is advancing towards initiation of IND enabling studies this year. We continue to expect to file an IND in the first half of 2024. Additionally, we continue to conduct early research on our tau gene silencing program, which we introduced earlier this year. This program utilizes a vectorized siRNA delivered with the TRACER capsid to reduce tau expression in the brain. Today, we are introducing another early research program in our Alzheimer's disease franchise. In this program, we are combining a vectorized anti-Aβ antibody with a TRACER capsid. I will turn the call over to Todd who will talk more about this program momentarily. But first, I want to explain why Voyager has chosen to focus three of our six wholly owned programs on Alzheimer's disease. On Slide 7, a glance across the top row highlights some of the recent progress with anti-amyloid antibodies. These represent tremendous first steps towards modifying the course of Alzheimer's disease. Turning to the second row of milestones on this slide, there’s an increasing body of data demonstrating the role of tau in Alzheimer's disease. I think of amyloid as a trigger and tau as the bullet. There’s a tipping point at which increasing amounts of amyloid cause tau to spread and that spread of tau is what causes neurodegeneration. The Lilly data reinforced this demonstrating that anti-amyloid treatment showed greater clinical benefit in patients with lower tau burden. Ultimately, we need to better understand the clinical efficacy of anti-amyloid treatments by stage and subtype. We may already be starting to see evidence of complete responders, partial responders, and non-responders to anti-amyloid treatment based on recent Phase 3 data. Complete responders may not need any further treatment than anti-amyloid. But partial responders may be appropriate for a combination of anti-amyloid and anti-tau therapies. And non-responders to anti-amyloid might be candidates for switching to anti-tau monotherapy. In short, this is a disease that affects millions of people. The field is making great progress against multiple targets, and there's still much work to be done. Now, I will turn the call over to Todd to talk about our new anti-amyloid gene therapy program.

Thank you, Al. Please turn to Slide 8. As Al mentioned, there are now multiple FDA approved anti-amyloid antibodies for Alzheimer's disease. We think a vectorized anti-amyloid gene therapy may offer the benefit of providing similar disease modifying efficacy with a single dose. Additionally, while more research is needed, there is biologic rationale to suggest that a gene therapy approach to targeting amyloid may reduce the risk of amyloid-related imaging abnormalities, or ARIA. In the gene therapy approach, the anti-amyloid antibodies are steadily secreted by cells in the central nervous system. And thus, we would be avoiding high antibody concentrations that necessarily follow intravenous antibody infusions. Moreover, the antibody would first engage the beta amyloid deposited in and around amyloid plaques, rather than beta amyloid deposited around blood vessels. Both mechanisms may reduce the risk of ARIA. Voyager has a long history of antibody expertise. Our lead program is our anti-tau antibody VY-TAU01. Although VY-TAU01 is not a gene therapy, we previously shared data at the Alzheimer's Association International Conference in 2022 demonstrating that we had vectorized antibodies from this program and achieved substantial anti-tau antibody expression in the hippocampus, cortex and CSF of mice, which was sustained seven months after a single administration. In addition, we have also vectorized an anti-HER2 antibody for the potential treatment of brain metastases from breast cancer. So this gives you a flavor for Voyager's work in antibodies as a whole and in vectorizing antibodies specifically. In this new program, we had vectorized an anti-Aβ antibody and delivered it using a novel capsid. Preliminary data in mice have shown target engagement with amyloid plaques following a single IV administration of the vectorized antibody with the BBB-penetrant capsid. We have shown this using vectorized mirroring antibodies and vectorized humanized antibodies. And we are currently evaluating antibody payloads with our tracer capsids. I'll now turn the call back to Al.

Thank you, Todd. Turning to Slide 9. As you can see, Voyager continues to execute on our milestones. We secured partnerships with Pfizer, Neurocrine, Novartis, and now Sangamo, and the company is well capitalized with approximately $273 million in cash on our balance sheet. We selected a development candidate for our anti-tau antibody program for Alzheimer's disease. And we launched three new early stage gene therapy programs, one for Huntington's disease and two for Alzheimer's disease. We also continue to add incredible talent to our team. Last quarter, we welcomed George Scangos to our Board of Directors. Earlier this month, we appointed Jacquelyn Fahey Sandell as our Chief Legal Officer, and she is already adding tremendous value. Looking forward, we continue our work to break through the barriers constraining the fields of gene therapy and neurology. We expect to identify a lead candidate for our wholly owned SOD1 ALS gene therapy program by the end of this year. 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, once clinical trials begin several shots on goal to establish human proof of concept for our TRACER capsids. Furthermore, there's potential to see early biomarker based evidence of disease impact in some of these very difficult CNS indications. We continue to engage in active discussions with potential partners regarding collaboration and licensing arrangements around our platform and pipeline. In summary, it's a very exciting time in Voyager, and we look forward to continued execution this year and next. With that, we're happy to take any questions you may have. Operator?

Thank you, presenters. Your first question comes from Joon Lee of Truist Securities. Please go ahead with your question.

Thanks for taking our questions. On the Alzheimer's program, are you able to share any information regarding the choice of the antibody that you plan to vectorize? And how do you plan to mitigate risks associated with ARIA, for example? And I know you mentioned specifically plaques that are not on vessels. And curious if there are certain antibodies you’re aware of that can do that? And lastly, would you be able to sit on an RNAi in the same contract? I'm thinking maybe a vectorized tau RNAi for a dual pronged strategy. And I have a quick follow up.

Thank you, Joon. This is Al Sandrock. We haven't disclosed which of the anti-amyloid antibodies we're going to vectorize yet. As you know, we have a choice of a few. And we're doing experiments too on several of them now, or at least more than one anyway. We will disclose that at the right time in the future. The risk of ARIA is real. And Todd nicely pointed out the reasons why we think we're going to minimize the risk of ARIA with our vectorized antibody. Nevertheless, it's something to keep in mind. There's two things I would say here. One is that the risk of ARIA is mostly in the first six months to one year of treatment. And so if ARIA were still a concern, we may wait until most of the risk has passed and therefore use the gene therapy as more of a maintenance after the initial treatment for 6 to 12 months. And then the second thing is that we have some preliminary experiments regulating gene expression with a small molecule which we may be able to then turn on or turn off or adjust the dose in the future. So both are things we are actually contemplating at this point. In terms of RNAi, you're right that we have a vectorized RNAi tau knockdown program. At the present time, we don't plan on combining the two into the same vector.

Got it. Thanks for that. And your deal was Sangamo, it's really interesting, because they got the license to your capsids for the prion disease. Yet, just a month later, Prevail, a subsidiary of Eli Lilly and now an agreement was Sangamo to develop a novel capsid for Prevail's Parkinson's program. It’s confusing and amusing at the same time. We would appreciate if you could elaborate a little bit on the deal, given your competitive position on a similar gene therapy program for Parkinson's. Thank you.

Yes. Thanks, Joon. Well, I really can't speak to Prevail’s strategy here. However, I can verify that Sangamo did come to us seeking the capsid for the prion disease program.

Then just a quick follow up. Obviously, are you concerned at all or are there mechanisms in place to ensure that whatever they may learn from your past that is not stays within Sangamo or maybe between you and Sangamo, but not lead to competitors?

Well, we trust Sangamo. I know the scientists and the CEO there very well. We think they'll take good care of our capsid as well as any of the intellectual property around them.

Thank you so much. Your next question comes from the line of Laura Chico of Wedbush. Please ask your question.

Hi. This is Ingrid on for Laura Chico. Thank you for taking our questions. One question for Pete. Pete, how should we be thinking about R&D expense trajectory as you're heading into 2024? You'll be in a position to file an IND. And so how much of a pickup should we be expecting here?

Ingrid, I appreciate the question. And we don't really provide tremendous guidance with regard to forward-looking burn or R&D expenses going forward into 2024 at this point. I would say this. If you do look at our R&D burn for the first six months of this year and in the most recent quarter, our burn is up about 50% plus on the R&D side. Overall, from a financial perspective, you see that that's coming off that perspective. From a cash flow perspective, our overall burn is kind of tracking and tracing to about 15% higher. That's on a six-month basis. So if you look at last year in 2022, our burn was $78 million for the full year. Our first six months of this year is $45 million on a net basis. That translates to that 15% increase. So hopefully that helps you.

Thank you. I appreciate that.

Ingrid, I understand your concern about our burn rate, and it's a valid concern. I want to assure you that we will continue to maintain financial discipline as these early stage programs require relatively low resources. We select programs based on our ability to quickly achieve proof of concept and mitigate risks in the clinic. I want to emphasize once again that we will continue to practice financial discipline and preserve a strong cash runway.

And Al, I agree with you wholeheartedly. I think that really shows in the cash balance that we have as the close of a quarter $273 million on the balance sheet. Good runway going forward. And we continue to reiterate that that carries us into 2025.

Thank you.

Thank you so much. Your next question comes from the line of Jack Allen of Baird. Please go ahead.

Congratulations to the team on all the progress made over the quarter and thanks for taking the question. I guess the one key question I have is around the tau antibody IND in the first half of next year. I guess any additional color you can provide as it relates to pre-IND activities that need to be completed to get that IND done and submitted?

Yes. So Jack, this is Al. We did have feedback from the FDA in the form of a pre-IND interaction earlier this year. And so our timelines are based on what we learned from that feedback and what more needs to be done to get to an IND. The main thing, of course, is the toxicology study, GLP tox studies that we will be initiating shortly as well as of course gearing up manufacturing so we can start dosing patients. And I'm happy to say that we're on track on all these fronts, and we continue to believe we'll file an IND in the first half of next year.

Great. Thanks so much.

Thank you so much. Your next question comes from the line of Phil Nadeau of TD Cowen. Please go ahead.

First on the SOD1 ALS gene therapy program. Can you discuss in a bit more detail the work you're doing to identify the lead candidate? What experiments in particular do you think will differentiate among the candidates that you have in development currently?

Great question. I’m going to ask Todd to answer that.

Thank you for the question. We are very enthusiastic about our capsids and their capability to cross the blood-brain barrier. We are currently working on identifying the best combination of the transgene with the most effective capsid. To determine the best candidate, we are conducting experiments in non-human primates.

And many of you might be asking about, how did you choose the particular siRNA?

I see. So our process, we have a long history of vectorizing siRNAs at Voyager. We have a process by which we first screen, identify siRNAs and then begin screening the vectorization components that we look at a whole variety of different characteristics. So we look at specificity for the gene, we look at the ability to knock it down with that specificity, making sure that we don't have substantial off-target effects. And all of those things come together to identify the optimal trans gene.

Yes. If I remember correctly, Todd, we used the mouse specific capsid with one of these vectorized siRNAs and got some very nice data in mouse models of SOD1 ALS.

That’s true. On the G93A SOD1 animal model, we saw greatly extended lifespan and motor capacity retained and we presented that at conferences as well.

That's really helpful. Then one last question from us. The slides note that there are discussions ongoing for potential partnerships. Can you give us some sense of what type of partnerships you're interested in? What do you think would create value for the company and shareholders?

Yes, thank you. As you can observe, we have a track record of engaging in various types of deals. On one end, we have a licensing agreement we established with Pfizer and Novartis, where our involvement is minimal after they select a capsid. They possess all the necessary capabilities in-house to advance those programs. Conversely, we have the collaboration with Neurocrine, which is a more integrated partnership focused on GBA1 and three undisclosed neuro targets, alongside previous arrangements for Friedreich's ataxia. In these cases, we act more as research collaborators. They cover our expenses, and we work closely with them, but they retain decision-making authority and manage the progress. We aim to be as collaborative and supportive as possible. These examples represent the two extremes, and we are open to exploring any arrangements in between. Ultimately, our goal is to assist patients while enhancing shareholder value over time, and we will pursue whatever approaches are sensible for both objectives.

That's really helpful. Thanks for taking our questions.

Thank you so much. Your next question comes from the line of Yanan Zhu of Wells Fargo Securities. Please ask your question.

Hi. Thanks for taking our questions. This is Quan on behalf of Yanan. I have a two-part question regarding the new anti-Aβ program. First, while I understand that you cannot disclose the asset, could you clarify whether you are targeting anti-Aβ monomer, oligomer, or fibrillar? Todd mentioned engagement with the plaque; does that imply it targets fibrillar? Second, I assume the tissue concentration you're aiming for may differ from the naked antibody strategy. What new concentration are you targeting, and what do you speculate the required dose level will be to achieve that concentration? Thank you.

I will take the first question and then ask Todd to address the second one. Regarding the antibody, we will not use antibodies to target the monomer, as they are ineffective. The data clearly shows that they have not worked. Instead, we will focus on antibodies that target soluble oligomers and insoluble fibrils. Examples include aducanumab and lecanemab, which are selective for aggregated forms of Aβ, including large soluble oligomers and the fibrillar amyloid found in amyloid plaques. We chose these because they have strong validation from human clinical trials and have received FDA approval, with one having been fully approved recently. So, there is a clear rationale for this approach. Todd, would you like to address the second question?

So I want to confirm that I heard the second one correctly. It's a question about the vectorized antibody and how it differs from the straight antibody. Is that right?

Right, and tissue concentration you plan to achieve and probably the dose level that might be required.

So I can't comment specifically on the tissue concentrations and the doses that we'll be going into. Clearly, we can see what the learnings are from the field on the antibody concentrations needed for efficacy. What we think a potential advantage of the vectorization is beyond the single dose, which of course could have implications for being able to treat large numbers of patients. But as we talked about in the call, we hope to avoid the potential reactions with ARIA that you get when you infuse an antibody, you necessarily get a peak of delivery, a peak of antibody exposure in the vascular system. We will be secreting in a constitutive fashion. So we hope to avoid that high exposure. And we hope that we expect to encounter the plaques in the brain before it's encountered in the blood vessels. We hope to have some advantage there as well.

Yes. So I guess the summary of that would be that we’re sort of targeting the area under the curve side of things rather than the Cmax that we achieve with antibodies because Cmax is more related to ARIA and AUC is more related to efficacy. I would also say that we know the concentrations in spinal fluid you have to achieve with both of those antibodies. And there is a typical range 0.1% to 0.5% brain-to-plasma ratio. And there's a lot of published information from animals as to what antibody concentrations are needed for removal of amyloid. So the nice thing is, this is a derisk program in many ways. We're going after a highly validated target. We have a lot of quantitative information that we can use for drug development. We understand the major side effects and thoughts about how to mitigate those. And that's the kind of thing that we like to go after, highly validated targets with efficient paths to proof of concept.

Got it. Super helpful. Thank you, Al and Todd.

Thank you so much. Your next question comes from the line of Matthew Hershenhorn of Oppenheimer. Please go ahead.

Guys, congrats on all the progress. This is Matt on for Jay. And thanks for taking our questions. So we were wondering if you had any thoughts following Biogen’s acquisition of Reata, which obviously reflects a pretty high value for the Friedreich's ataxia opportunity. So how are you thinking about any differentiating factors for your FA gene therapy program? Obviously, pros and cons potentially versus SKYCLARYS which you have collaborated with Neurocrine, and then the advantages as a potential later follower? And then for Pete, if you could just please remind us any timing on the potential for milestones in that FA program, that would be very helpful? Thank you both.

I'll start and then ask Pete to discuss the milestones. I was excited to see Biogen acquire Reata. Reata was the first drug ever approved for Friedreich's ataxia and shows evidence of disease modification by slowing progression. This was published in the Annals of Neurology, and I found the data compelling when I first reviewed the paper. I believe this is a breakthrough, and I hope we can continue this momentum and make further advances. With Friedreich's ataxia, the complexity arises because it involves both the central nervous system and the heart, but the Reata drug primarily targets the CNS as the outcomes measured were focused on neurological results. This program is currently under the management of Neurocrine, and having regulatory precedents set by another company, with accepted outcome measures, can only be beneficial. Our goal is to address the gene replacement since it's an autosomal recessive condition, meaning patients with the disease do not produce frataxin. We need to find a way to replace frataxin, and our strategy is gene therapy. It's crucial to determine the correct dosage because too much frataxin may also be harmful. Ultimately, this responsibility lies with our colleagues at Neurocrine, and I'll let them provide more detailed information regarding the program.

Matt, with regards to specific guidance on milestones associated with the FA program, which I think was the second part of your question, so what we've provided in the past is kind of a full summary of what the 2019 Neurocrine agreement looks like in terms of future milestones. Those milestones are about $1.4 billion approximately. We have not guided or provided detailed guidance with regards to what the specific next milestones are on that program. But I do think what I would highlight, not just for Neurocrine but also for some of our other partnerships, we do have a number of milestones that potentially could come due in the next couple of years here on all those partnerships. As Al alluded to earlier, we've got 11 partner programs now, seven with Neurocrine alone, three in the original 2019 agreement, which includes FA. Those milestones have not been factored into our cash runway as of yet and potentially could benefit us greatly as we move forward here. So that would be what I would say with regards to that.

Okay, very helpful. I really appreciate the answer. Thanks and congrats again.

Thanks, Matt.

And our next question comes from the line of Ross Fladeland of Canaccord Genuity. Please go ahead.

Ross on for Sumant Kulkarni. I've got a question in regards to the antibody programs you have going on. Given that you now have an anti-tau antibody and also a vectorized anti-tau antibody program, what does this mean in context for prioritizing spend levels on relatively expensive Alzheimer's programs versus the other programs in your pipeline? Thank you.

Yes. Thanks for the question. So actually we do not have a vectorized antibody against tau program. We have essentially a passive intravenously administered antibody, monoclonal antibody vectorized. After we achieve proof of biology hopefully, we will achieve that. And if we do, we have a choice then of moving forward with either continuing with the passive antibody or going to vectorization. So I just want to clarify that. And the whole approach here is to choose programs where we can get proof of biology very efficiently. For example, in the antibody to tau, we think we can do a proof of biology experiment in humans with about 25 patients per dose group in a one year study. And with tau PET imaging, we think we can determine whether we block the spread of pathological tau. And so we like that, because it's a rapid path to derisking and proof of biology. And then after that, as I said, we have a choice of vectorizing or not. I hope that clarifies or answers your question.

Yes. Thank you.

Thank you so much. And presenters, there are no further questions at this time. I would now like to turn the conference back to you for closing remarks.

Thank you very much for all the great questions. If you have any further inquiries, please feel free to contact us, and we'll do our best to provide answers. We appreciate your interest in Voyager.

Thank you, presenters. This concludes today's conference call. Thank you for participating and you may now disconnect. Have a good day.