Evidence map›Paper›PMID 39444037›Full record

Trial reportAlzheimer's research & therapy2024

Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.

Hua Long, Adam Simmons, Arthur Mayorga, Brady Burgess, Tuan Nguyen, Balasubrahmanyam Budda, Anna Rychkova, Herve Rhinn, Ilaria Tassi, Michael Ward and 5 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03635047 (A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL002 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03635047 phase1completednot on this map

A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL002 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorAlector Inc.Ran2018 to 2020Enrolled69ConditionsHealthy, Alzheimer DiseaseArmsAL002, Saline Solution
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  10. TREM2-Targeting peptide tracer for neuroinflammation PET imaging.European journal of nuclear medicine and molecular imaging · 2026
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Hua Long *Alector, Inc., South San Francisco, CA, 94080, USA.
Adam Simmons *Alector, Inc., South San Francisco, CA, 94080, USA. Adam.Simmons@alector.com.
Arthur MayorgaAlector, Inc., South San Francisco, CA, 94080, USA.
Brady BurgessAlector, Inc., South San Francisco, CA, 94080, USA.
Tuan NguyenAlector, Inc., South San Francisco, CA, 94080, USA.
Balasubrahmanyam BuddaAlector, Inc., South San Francisco, CA, 94080, USA.
Anna RychkovaAlector, Inc., South San Francisco, CA, 94080, USA.
Herve RhinnAlector, Inc., South San Francisco, CA, 94080, USA.
Ilaria TassiAlector, Inc., South San Francisco, CA, 94080, USA.
Michael WardAlector, Inc., South San Francisco, CA, 94080, USA.
Felix YehAlector, Inc., South San Francisco, CA, 94080, USA.
Tina SchwabeAlector, Inc., South San Francisco, CA, 94080, USA.
Robert PaulAlector, Inc., South San Francisco, CA, 94080, USA.
Sara Kenkare-MitraAlector, Inc., South San Francisco, CA, 94080, USA.
Arnon RosenthalAlector, Inc., South San Francisco, CA, 94080, USA.

Funding

Alector N/A
6 · The paper itself

Abstract

backgroundVariants of the gene triggering receptor expressed on myeloid cells-2 (TREM2) increase the risk of Alzheimer's disease (AD) and other neurodegenerative disorders. Signaling by TREM2, an innate immune receptor expressed by microglia, is thought to enhance phagocytosis of amyloid beta (Aβ) and other damaged proteins, promote microglial proliferation, migration, and survival, and regulate inflammatory signaling. Thus, TREM2 activation has potential to alter the progression of AD. AL002 is an investigational, engineered, humanized monoclonal immunoglobulin G1 (IgG1) antibody designed to target TREM2. In AD mouse models, an AL002 murine variant has been previously shown to induce microglial proliferation and reduce filamentous Aβ plaques and neurite dystrophy.

methodsPreclinical studies assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL002 in cynomolgus monkeys. INVOKE-1 (NCT03635047) was a first-in-human phase 1, randomized, placebo-controlled, double-blind study assessing the safety, tolerability, PK, and PD of AL002 administered as single ascending doses (SAD) in healthy volunteers.

resultsIn cynomolgus monkeys, weekly intravenous injections of AL002 for 4 weeks were well tolerated, dose-dependently decreased soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) and total TREM2 in hippocampus and frontal cortex, and increased biomarkers of TREM2 signaling in CSF and brain. In the phase 1 study of 64 healthy volunteers, a single intravenous infusion of AL002 demonstrated brain target engagement based on a dose-dependent reduction of sTREM2 in CSF and parallel increases in biomarkers of TREM2 signaling and microglia recruitment. Single-dose AL002 showed central nervous system penetrance and was well tolerated, with no treatment-related serious adverse events over 12 weeks.

conclusionsThese findings support the continued clinical development of AL002 for AD and other neurodegenerative diseases in which TREM2 activation may be beneficial. AL002 is currently being tested in a phase 2, randomized, double-blind, placebo-controlled study in early AD.

trial registrationClinicaltrials.gov, NCT03635047. Registered on August 15, 2018, https://www. CLINICALTRIALS: gov/study/NCT03635047 .

Indexed as

Alzheimer DiseaseMacaca fascicularisMembrane GlycoproteinsReceptors, ImmunologicAdultAnimalsAntibodies, Monoclonal, HumanizedDouble-Blind MethodDrug Evaluation, PreclinicalFemaleHumansMaleMiddle AgedYoung AdultAntibodies, Monoclonal, HumanizedMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanAlzheimer’s diseaseBiomarkersMicrogliaPhase 1 clinical trialTREM2

Identifiers

PMID39444037
PMCPMC11515656

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.