Latozinemab
phase 3drug program · high · Fri Dec 08 2023 00:00:00 GMT+0000 (Coordinated Universal Time)
Provide a therapeutic program for frontotemporal dementia linked to progranulin deficiency and evaluate AL001 in C9orf72-associated ALS; continuation access is available for prior latozinemab study participants.
Clinical monoclonal-antibody drug program evaluated in phase 1, phase 2 open-label/controlled, phase 3 double-blind placebo-controlled, and continuation studies.
Continuation study for prior latozinemab participants published on ClinicalTrials.gov on 2023-12-08; phase 3 INFRONT-3 evaluates AL001 in participants at risk for or with frontotemporal dementia due to heterozygous progranulin gene mutations.
AL101 progranulin-elevating antibody
phase 1drug program · high · Sat Dec 14 2019 00:00:00 GMT+0000 (Coordinated Universal Time)
Elevate progranulin as a potential treatment approach for Alzheimer's disease and other neurodegenerative conditions where progranulin may play a role.
Monoclonal antibody that binds sortilin receptor, decreases cell-surface sortilin, partially blocks sortilin-progranulin interaction, and increases progranulin in blood and CSF; evaluated in in vitro, rat, nonhuman primate, and phase 1 healthy-volunteer studies.
Phase 1 first-in-human study assessed safety, tolerability, bioavailability, pharmacokinetics, and pharmacodynamics; publication reports AL101 increased plasma and CSF progranulin after single and multiple doses.
Cell assays showed increased progranulin through sortilin modulation. Rat and monkey studies showed decreased cell-surface sortilin and progranulin increases up to 2-fold in CSF and up to 4-fold in blood. Phase 1 healthy-volunteer dosing produced significant plasma and CSF progranulin increases.
AL003 Alzheimer's disease first-in-human program
phase 1drug program · medium · Fri Mar 29 2019 00:00:00 GMT+0000 (Coordinated Universal Time)
Assess AL003 as a therapeutic candidate in healthy adults and patients with mild to moderate Alzheimer's disease.
Multi-center, randomized, double-blind, placebo-controlled dose-escalation first-in-human study assessing safety, immunogenicity, tolerability, pharmacokinetics, and pharmacodynamics.
First-in-human clinical trial record published on ClinicalTrials.gov on 2019-03-29.
AL002 TREM2 agonistic antibody
phase 2drug program · high
Treat early Alzheimer's disease by engaging TREM2 to regulate microglial function and disease biology.
Humanized TREM2 agonistic monoclonal antibody administered intravenously in randomized, double-blind, placebo-controlled phase 1, phase 2, and long-term extension clinical studies.
A 2026 phase 2 randomized trial publication reported sustained target engagement and pharmacodynamic responses but did not meet the primary endpoint in early Alzheimer's disease.
AL002 reduced soluble TREM2 and increased CSF osteopontin, indicating target engagement and pharmacodynamic activity, but the phase 2 trial was negative on Clinical Dementia Rating-Sum of Boxes change versus placebo; frequent adverse events included MRI changes resembling ARIA.
MS4A4A/MS4A6A-TREM2 microglia research program
exploratoryresearch program · medium
Identify and validate MS4A4A and MS4A6A as regulators of TREM2 and microglial function, and as potential drug targets for Alzheimer's disease.
Knockout, overexpression, degrading-antibody, macrophage, microglia, nonhuman-primate, and amyloid-pathology mouse-model studies of MS4A4A/MS4A6A effects on TREM2, soluble TREM2, microglial viability, phagocytosis, and lysosomal function.
A 2026 Neuron publication reported that MS4A4A and MS4A6A cooperate as post-transcriptional negative regulators of TREM2 and microglial function.
MS4A4A and MS4A6A negatively regulated transmembrane and soluble TREM2; MS4A4A limited microglia viability, phagocytosis, and lysosomal function. The study proposed the pathway as a potential Alzheimer's disease drug-target area.
