Vaccinex, Inc. announced that it has completed enrollment goal in the SIGNAL-AD clinical trial for people with mild dementia due to Alzheimer's Disease (NCT04381468). Topline data from the study are expected in mid-2024, after the last enrolled patients will have received 12 months of treatment. The randomized, double-blinded, placebo-controlled Phase 1b/2 SIGNAL-AD study was designed to evaluate the safety, tolerability and effects on cognition and brain metabolism of the SEMA4D inhibitor, pepinemab.

The one-year study enrolled 40 patients with mild Alzheimer's dementia. The SIGNAL-AD study was designed to build on the data obtained in the Phase 2 SIGNAL study of pepinemab in Huntington's disease (HD), another neurodegenerative disease with many similarities in pathology to AD. Data from the SIGNAL-HD.

The SIGNAL-AD study was designed to evaluate the treatment of pepinemab in patients with mild AD. The randomized, double-blinded, placebo-controlled study enrolled 40 patients at 16 sites in the U.S. Patients were randomized 1:1 to receive pepinemab, administered as an intravenous infusion (IV) every 4 weeks for 44 weeks (12 infusions at 40 mg/kg). The study is 52 weeks in duration, including a safety and efficacy evaluation four weeks after the last dose of study drug.

Outcome measures include safety, an evaluation of brain metabolism and a battery of standard cognitive assessments specific to AD. Additional outcomes include measures of pepinemab immunogenicity and biomarkers associated with NDD including neurofilament light chain (NfL), Aß amyloid, tau, and immune and inflammatory markers. Vaccinex received funding support for this trial from the Alzheimer's Drug Discovery Foundation and the Alzheimer's Association under its Part the Cloud Program.

Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates the actin cytoskeleton of cells that plays an important role in inflammatory reactions in the brain as well as in tumor immune evasion. Data show that by preventing deleterious inflammatory gliosis during disease progression, pepinemab preserves normal function of astrocytes and microglia, two types of glial cells that play a crucial role in the function and health of neurons in the brain. Additional preclinical and clinical data show that pepinemab promotes infiltration and activation of dendritic cells and CD8+ T cells and reverses immunosuppression within the tumor microenvironment.

Pepinemab is being evaluated in several studies in neurodegenerative disease and oncology. Pepinemab has been administered to more than 400 patients and appears to have a favorable safety and tolerability profile.