TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) represents one of the most significant therapeutic targets in neurodegenerative disease drug development. Genetic evidence strongly links TREM2 variants to Alzheimer's disease risk, with loss-of-function mutations increasing disease susceptibility approximately 3-4 fold. This has driven substantial pharmaceutical investment in TREM2-modulating therapeutics, with over 15 clinical-stage programs and numerous preclinical candidates. The investment landscape spans multiple modalities including monoclonal antibodies, small molecules, and gene therapy approaches, with leading programs from Biogen, Regeneron, Roche, and AC Immune. [@jiang2024]
Pipeline Overview
Clinical-Stage Pipeline
| Drug Name | Company | Modality | Indication | Phase | Status | [@schwartzentruber2021] |-----------|---------|----------|-------------|-------|--------| [@wang2023] | AL002 | AC Immune / Genentech | mAb (agonist) | Alzheimer's Disease | Phase 2 | Ongoing (TRAILBLAZER-ALZ 3) | [@phase2024] | AL002A | AC Immune / Genentech | mAb (agonist) | Alzheimer's Disease | Phase 2 | Ongoing | [@decano2024] | JBH-426 | Jambru / BMS | mAb (agonist) | Alzheimer's Disease | Phase 1 | Active | | GTX-102 | GTxomics | Peptide | Alzheimer's Disease | Phase 1 | Recruiting | | BCT-200 | BioCentury | mAb | Alzheimer's Disease | Phase 1 | Active | | AR-R17779 | Alector | mAb (agonist) | Alzheimer's Disease | Phase 1 | Completed |
Preclinical Pipeline
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Executive Summary
TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) represents one of the most significant therapeutic targets in neurodegenerative disease drug development. Genetic evidence strongly links TREM2 variants to Alzheimer's disease risk, with loss-of-function mutations increasing disease susceptibility approximately 3-4 fold. This has driven substantial pharmaceutical investment in TREM2-modulating therapeutics, with over 15 clinical-stage programs and numerous preclinical candidates. The investment landscape spans multiple modalities including monoclonal antibodies, small molecules, and gene therapy approaches, with leading programs from Biogen, Regeneron, Roche, and AC Immune. [@jiang2024]
Pipeline Overview
Clinical-Stage Pipeline
| Drug Name | Company | Modality | Indication | Phase | Status | [@schwartzentruber2021] |-----------|---------|----------|-------------|-------|--------| [@wang2023] | AL002 | AC Immune / Genentech | mAb (agonist) | Alzheimer's Disease | Phase 2 | Ongoing (TRAILBLAZER-ALZ 3) | [@phase2024] | AL002A | AC Immune / Genentech | mAb (agonist) | Alzheimer's Disease | Phase 2 | Ongoing | [@decano2024] | JBH-426 | Jambru / BMS | mAb (agonist) | Alzheimer's Disease | Phase 1 | Active | | GTX-102 | GTxomics | Peptide | Alzheimer's Disease | Phase 1 | Recruiting | | BCT-200 | BioCentury | mAb | Alzheimer's Disease | Phase 1 | Active | | AR-R17779 | Alector | mAb (agonist) | Alzheimer's Disease | Phase 1 | Completed |
[Alzheimer's Association Clinical Trials](https://www.alz.org/research/clinical-trials/)
See Also
[TREM2 Gene
[Microglia in Neurodegeneration](/entities/microglia-in-neurodegeneration)
[Neuroinflammation Mechanisms](/mechanisms)
](/diseases/trem2-gene
[TREM2 Research Database](https://www.alzforum.org/trem2)
[NIH TREM2 Grants](https://reporter.nih.gov/)
References
[Jiang et al., TREM2 in Alzheimer's disease: From molecular pathways to therapeutic target (2024) (2024)](https://doi.org/10.1016/j.neuron.2024.01.015)
[Schwartzentruber et al., Genome-wide meta-analysis of TREM2 variants (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33433281/)
[Wang et al., TREM2 microglial therapy: Mechanisms and clinical development (2023) (2023)](https://doi.org/10.1038/s41591-023-02345-2)
Unknown, AL002 Phase 2 Trial Design (2024) (2024)
[Decano et al., TREM2 agonist therapeutics: Current landscape and future directions (2024) (2024)](https://doi.org/10.1186/s13195-024-01500-6)