Voyager Therapeutics, Inc.

for Alzheimer's disease and SOD1 gene therapy program for ALS. We currently have three wholly owned assets targeting Alzheimer's disease, including a new early research initiative just announced today to advance a vectorized anti-A-beta 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 partnered 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 am increasingly excited about the potential here to expand the reach of our technology into other approaches of neurogenetic medicine. Moving to slide five, 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 significant investment of time or money from Voyager. Moving up the slide, the seven programs depicted in yellow represent our collaborative programs with Nurocrine. For these programs, Voyager is fully reimbursed for our collaborative research. The six programs depicted in orange at the top of the slide represent our Hoi On pipeline. This is where I will focus today. Turning to slide six, 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 a 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-A beta 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 seven, a glance across the top row highlights some of the recent progress with anti-amyloid antibodies. These represent tremendous first steps toward 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 the 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 versions. 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 III 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-TAL therapies. and non-responders to anti-amyloid might be candidates for switching to anti-tyl-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'll turn the call over to Todd to talk about our new anti-amyloid gene therapy program.

Thank you, Al. Please turn to slide eight. 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 a 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 the 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-tau-01. Although VY-tau-01 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 have vectorized an anti-A-beta 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 a BBB penetrant capsid. We have shown this using vectorized murine 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 Skangos to our board of directors. Earlier this month, we appointed Jacqueline Fahy 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 is 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 at 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?