Anti-Tau Agent VY7523 Demonstrates Positive Safety in Early Alzheimer Trial

Toby Ferguson, MD, PhD

Newly announced data from a single-ascending dose (SAD), phase 1, placebo-controlled trial showed that treatment with investigational VY7523 (Voyager Therapeutics), an anti-tau therapy in development for Alzheimer disease (AD), was well tolerated across several different dose cohorts of healthy volunteers. The therapy is also currently being assessed in a multiple-ascending dose (MAD) trial, with initial tau PET imaging data expected in the second half of 2026.¹

In this randomized, double-blind study, VY7523 was well accepted by a cohort of 48 healthy volunteers, meeting its primary objective of safety, with no serious adverse events (AEs) across 6 dose levels. Investigators also recorded no severe AEs or infusion reactions with the intravenously administered, recombinant, humanized IgG monoclonal antibody. The trial met secondary objectives, showing dose-proportionate serum concentration increases and a CSF-to-serum ratio of 0.3%, aligning with approved AD monoclonal antibodies.

"We continue to view tau as the most exciting target in Alzheimer disease, which is why we are advancing two tau-targeting approaches, our anti-tau antibody and our tau silencing gene therapy,” Toby Ferguson, MD, PhD, chief medical officer at Voyager, said in a statement. "For the antibody approach, we believe VY7523 could be best-in-class due to the emerging PK data and previous preclinical data showing 70% reduction in tau spread, as well as its specificity for pathological tau and for a unique C-terminal epitope. We look forward to third-party data later this year and early next year, which could continue to build excitement around tau ahead of our VY7523 tau PET data."

The MAD trial, which expects to have data in mid-2026, features 52 patients with early AD, using safety and tolerability as the primary end point. This double-blind, randomized, placebo-controlled study also tests VY7523’s ability to limit the spread of pathological tau as a secondary end point, along with other immunogenicity and pharmacokinetic parameters.

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In a previously conducted mouse seeding model study, treatment with the anti-tau antibody inhibited the spread of pathological tau by more than 70%. Presented at the 2022 Alzheimer’s Association International Conference (AAIC), the preclinical study screened 728 anti-tau antibodies from human AD brains, selecting 4 (AB01, AB03, AB04, AB05), based on novel sequences, functional inhibition, and developability. In mice, all reduce tau pathology spread, with AB01 showing the greatest efficacy.²

At AD/PD 2024, investigators presented pharmacokinetic (PK) and tolerability data of VY7523 in nonhuman primate models (NHM), characterizing single intravenous (IV) dose at a high or mid-level. Results showed no adverse effects following the drug’s administration that would indicate the presence of PK-altering anti-drug antibody response. More notably, serum and cerebrospinal fluid concentrations increased with increasing dose levels in an approximately dose proportional manner.³

In the 7-week PK study, the serum half-life of VY7523, otherwise known as VY-TAU01 at the time, was approximately 12 days. VY7523 CSF distribution was approximately 0.1-0.2% of serum exposure typical of monoclonal antibody distribution to the CSF. Additionally, clearance and steady state apparent volume of distribution parameters from the serum PK analysis were typical of a human IgG4 monoclonal antibody administered to a monkey, demonstrating modest clearance and a volume of distribution consistent with distribution to serum and interstitial fluid.

REFERENCES
1. Voyager Reports Positive Topline Data for Single Ascending Dose (SAD) Trial of Anti-Tau Antibody VY7523 and Initiates Multiple Ascending Dose (MAD) Trial in Alzheimer’s Disease. News release. Voyager Therapeutics. March 3, 2025. Accessed March 3, 2025. https://www.globenewswire.com/news-release/2025/03/03/3035441/36461/en/Voyager-Reports-Positive-Topline-Data-for-Single-Ascending-Dose-SAD-Trial-of-Anti-Tau-Antibody-VY7523-and-Initiates-Multiple-Ascending-Dose-MAD-Trial-in-Alzheimer-s-Disease.html
2. Liu W, Kurella V, Liu L, et al. Identification and characterization of novel anti-tau antibodies that inhibit tau-seed mediated pathology in a PS01S tauopathy mouse model of Alzheimer’s disease and tauopathies. Presented at: 2022 Alzheimer’s Association International Conference. ABSTRACT 62878
3. Liu W, Kundu J, Emery MG, et al. Pharmacokinetics and Tolerability of VY-TAU01, an Anti-tau Antibody for the Treatment of Alzheimer’s Disease, in P301s Mouse and Nonhuman Primate. Presented at: ADPD 2024; March 5-9; Lisbon, Portugal.