SOUTH SAN FRANCISCO, Calif.—Alector Inc., a clinical stage biotech focused on immuno-neurology, reported recently safety and biomarker data from the single ascending dose (SAD) phase of the INVOKE Phase1 study of its product candidate, AL002, in healthy volunteers. AL002 is a monoclonal antibody intended to enhance the activity of TREM2 and is being developed by Alector for the treatment of Alzheimer’s disease in collaboration with its partner AbbVie. The data were presented at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) that was held in late 2019 in San Diego.
The AL002 presentation at CTAD showcases the first data in humans showing that a TREM2 activating antibody engages its target and demonstrates downstream activity in the central nervous system. Dr. Robert Paul, chief medical officer of Alector, presented an abstract entitled “A Phase 1 Study of AL002 in Healthy Volunteers and Patients With Mild-To-Moderate Alzheimer’s Disease” during an oral communications session.
The INVOKE clinical study is a first-in-human study in healthy adults and in patients with mild to moderate Alzheimer’s disease, designed to assess the safety (including immunogenicity) and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL002. The data reported today are from the study’s SAD phase in 56 healthy adults, who were enrolled into nine escalating dose cohorts.
Highlights from the SAD portion of the Phase 1 INVOKE study include:
- Fifty-six healthy volunteers were treated with nine escalating doses of AL002
- AL002 was found to be generally safe and well-tolerated
- AL002 reduced cerebrospinal fluid (CSF)-soluble TREM2 in a dose-dependent manner, demonstrating proof-of-target engagement in the brain
- AL002 elevated a biomarker for microglia activity in the CSF, indicating proof-of-mechanism
The Phase 1b portion of the study in Alzheimer’s disease patients is on-going. Alector expects to initiate the AL002 Phase 2, proof-of-concept study in 2020
“Loss of TREM2 activity has been shown through human genetics to be one of the major risk factors of developing Alzheimer’s disease,” said Paul. “AL002 is the first TREM2 agonistic antibody in clinical development for Alzheimer’s disease, and we are pleased to see safety and tolerability in healthy volunteers and that AL002 is showing proof-of-target engagement and proof-of-mechanism at this early stage in development. These results together will help guide our dose selection for the Phase 2 study in Alzheimer’s patients.”
