Abstract Details

Title A Phase 1 Study of AL003 in Healthy Volunteers and Participants with Alzheimer’s disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-002

Objective

The Phase 1 study assessed safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL003 in healthy volunteers (HV) and patients with mild to moderate AD.

Background

AL003 is a human anti-CD33 monoclonal antibody developed for the treatment of Alzheimer’s disease (AD). CD33 regulates uptake of the amyloid β1-42 (Aβ42) peptide by myeloid cells, and effective phagocytosis of Aβ42 correlates with low functional expression of CD33. AL003 specifically binds to and downregulates CD33 in preclinical models and provides an immune-mediated mechanism to treat AD.

Design/Methods The single ascending dose (SAD) part of the study was a blinded, randomized, placebo-controlled, study of single dose intravenous (IV) AL003 in HV in doses ranging from 0.05 mg/kg up to 60 mg/kg. The second part of the study assessed 15mg/kg AL003 or placebo administered every four weeks for two doses in a blinded, randomized, placebo-controlled manner in patients with a diagnosis of probable AD, aged 50-85 years, MMSE score of 16-28, CDR global score of 0.5, 1, or 2, and positive amyloid-PET scan. Both parts of the study included standard clinical safety measures, PK and PD markers.

Results The SAD portion completed assessment of all dose levels. The most frequently reported adverse events were headache (20.7%), post-lumbar puncture syndrome (i.e., headache after lumbar puncture; 17.2%), nausea (13.8%), upper respiratory tract infection (13.8%), and puncture site pain (10.3%). Dose levels up to 15 mg/kg were well tolerated in HVs with immune-related adverse events at higher dose levels. Peripheral PK and PD in HV were dose-dependent and CSF PD data established evidence of target engagement.

Conclusions AL003 was generally safe and well tolerated and the Phase 1 HV data demonstrated target engagement in peripheral and central nervous system compartments up to 60 mg/kg. AL003 is being considered for investigation in a proof-of-concept Phase 2 study.

Authors/Disclosures
PRESENTER	No disclosure on file
Robert Paul, MD, PhD	Dr. Paul has received personal compensation for serving as an employee of Alector. Dr. Paul has received stock or an ownership interest from Alector.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Glenn Morrison, PhD (Annexon Biosciences)	Dr. Morrison has received personal compensation for serving as an employee of Alector. Dr. Morrison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG . Dr. Morrison has stock in Alector. Dr. Morrison has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Michael Ward	Michael Ward has received personal compensation for serving as an employee of Alector. Michael Ward has stock in Alector. Michael Ward has received intellectual property interests from a discovery or technology relating to health care. Michael Ward has a non-compensated relationship as a Reviewer with ADDF that is relevant to AAN interests or activities.

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