Background

This is a humanized monoclonal anti-tau IgG antibody that recognizes a conformational epitope in tau oligomers. It was generated by immunizing mice with oligomers encapsulated in artificial lipid vesicles, in an effort to elicit antibodies that would bind to, and clear, tau oligomers from synapses.

According to data in a bioRxiv preprint from Aprinoia scientists, the mouse version of the antibody binds more avidly to tau in synaptosome and insoluble fractions of human brain extracts than to monomeric, cytosolic tau. The antibody reacted with tau aggregates from early stage AD cases, but not with tangles and neuropil threads that form later in the disease (Tai et al., 2022). It recognized aggregates of both the 3R and 4R tau splice forms, including those in Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy.

In preclinical work reported in the same manuscript, the antibody reacted with tau aggregates in rTg4510 mice expressing P301L tau. The antibody recognized tau in distal neurites in young mice, and later, in cell bodies. APNmAb005 blocked the transmission of pathogenic tau in cells treated with rTg4510 mouse brain extracts. Twelve weeks of antibody injection partially rescued synaptic and neuronal loss in the hippocampus without changing overall tau levels.

Findings

In May 2022, Aprinoia began a Phase 1, first-in-human study. It will enroll 40 healthy people in five dosing groups to receive single intravenous infusions of 5, 10, 25, 50 or 70 mg/kg, or placebo. Adverse events, vital signs, electrocardiograms, clinical lab measures, and study discontinuations will be tracked for 70 days after each dose, before proceeding to the next-highest dose. Other outcomes include pharmacokinetics and antidrug antibodies, as well as plasma and CSF Tau and phosphoTau-181, -217, and -231. Completion is expected in January 2023.

Aprinoia is also developing a PET tracer, now in Phase 2 trials in the U.S., and Phase 3 in China (company pipeline; Mar 2020 news; Feb 2020 news).

In January 2023, this private company merged with a special-purpose acquisition company to create a publicly traded corporation focused on neurodegenerative diseases (press release).

For details on this trial, see clinicaltrials.gov.