Background

VY-TAU01 is a recombinant, humanized IgG4 monoclonal antibody to an epitope in the C-terminus of tau. It is designed to block the spread of pathological tau.

According to a poster presented at AAIC 2022, this antibody was generated by immunizing mice with paired helical filamentous tau isolated from human brain. More than 700 monoclonal antibodies were screened for selectivity to pathological tau, as well as for their ability to inhibit seeding of tau aggregates in vitro and spreading of tau pathology in mice. Voyager presented data demonstrating that the most efficacious C-terminal antibody, Ab01, inhibited the spread of pathological tau by greater than 70 percent in the P301S mouse seeding model. This mouse IgG1 antibody was subsequently humanized to generate the clinical candidate (AD/PD 2023 conference poster).

In nonhuman primates, blood levels after intravenous administration were dose-proportional. The antibody’s half-life was 11-12 days, CSF exposure was approximately 0.1-0.2 percent of serum (AD/PD 2024 poster). There was no indication of a significant anti-drug antibody response.

Findings

On May 16, 2024, Voyager announced the start of clinical development with a single-ascending-dose safety and pharmacokinetic study of intravenous VY-TAU01 (press release). The trial expects to enroll 48 healthy volunteers in multiple dose cohorts. The trial was not found in registries.