TABLE 3.
Agents in Phase 1 of Alzheimer's disease drug development (ClinicalTrials.gov accessed January 1, 2023).
| Agent | Therapeutic purpose | CADRO target | Mechanism of action | Clinical trial NCT# | Lead sponsor | Start Date | Estimated Primary Completion Date |
|---|---|---|---|---|---|---|---|
| ACU193 | DMT, biologic | Aβ | Monoclonal antibody targeting soluble AB oligomers | NCT04931459 | Acumen Pharmaceuticals | Jun 2021 | Mar 2023 |
| Allopregnanolone | DMT, small molecule | Neurogenesis | Allosteric modulator of GABA‐A receptors | NCT03748303 | University of Arizona | Oct 2019 | Dec 2022 |
| ALN‐APP | DMT, biologic | Aβ | RNAi to decrease APP and downstream Aβ‐related events | NCT05231785 | Alnylam Pharmaceuticals | Feb 2022 | Jul 2025 |
| ALZ‐101 | DMT, biologic | Aβ | Aβ‐directed vaccine | NCT05328115 | Alzinova AB | Sep 2021 | Jul 2023 |
| APNmAb005 | DMT, biologic | Tau | Anti‐tau antibody | NCT05344989 | APRINOIA Therapeutics, LLC | May 2022 | Jan 2023 |
| ASN51 | DMT, small molecule | Tau | O‐GlcNAcase inhibitor | NCT04759365 | Asceneuron Pty Ltd. | Jun 2021 | Dec 2022 |
| AV‐1959 | DMT, biologic | Aβ | Anti‐amyloid vaccine | NCT05642429 | Institute for Molecular Medicine | Feb 2023 | Feb 2026 |
| Cannabidiol | Sx, behavior | Neurotransmitter receptors | Cannabinoid | NCT04075435 | Mclean Hospital | Jan 2021 | Jan 2023 |
| Centella asiatica | DMT, small molecule | Synaptic plasticity/neuroprotection | Antioxidant and anti‐inflammatory agent with synaptic and neuroprotective effects | NCT05591027 | Oregon Health and Science University | Nov 2022 | Oct 2024 |
| CMS121 | DMT, small molecule | Oxidative stress | Fatty acid synthase inhibitor | NCT05318040 | Virogenics, Inc. | May 2022 | Dec 2022 |
| CpG1018 | DMT, biologic | Inflammation | Toll‐like receptor 9 agonist leading to reduced Aβ plaques and tau pathology | NCT05606341 | NYU Langone Health | Nov 2022 | Nov 2024 |
| Donepezil | Sx, cognition | Neurotransmitter receptors | Cholinesterase inhibitor | NCT04730635 | Merck Sharp & Dohme LLC | Mar 2021 | Jan 2023 |
| Emtricitabine | DMT, small molecule | Inflammation | Nucleoside reverse transcriptase inhibitor (NRTI) | NCT04500847 | Butler Hospital | Dec 2021 | Mar 2023 |
| GB‐5001 | Sx, cognition | Neurotransmitter receptors | Cholinesterase inhibitor | NCT05525780 | G2GBio, Inc. | Aug 2022 | Aug 2023 |
| IBC‐Ab002 | DMT, biologic | Inflammation | Anti‐programmed death‐ligand 1 (PD‐L1) immune checkpoint inhibitor | NCT05551741 | Immunobrain Checkpoint | Oct 2022 | Oct 2024 |
| Lecanemab | DMT, biologic | Aβ | Anti‐amyloid monoclonal antibody | NCT05533801 | Eisai Inc. | Sep 2022 | Feb 2023 |
| Lu AF87908 | DMT, biologic | Tau | Anti‐tau monoclonal antibody | NCT04149860 | H. Lundbeck A/S | Sep 2019 | Jun 2023 |
| LX1001 | DMT, biologic | apoE, lipids, and lipoprotein receptors | Adeno‐associated virus (AAV) gene transfer vector expressing the cDNA coding for human APOE ε2 directly to the CNS/CSF of APOE ε4 homozygotes | NCT05400330 | Lexeo Therapeutics | Nov 2022 | Dec 2027 |
| LY3372993 | DMT, biologic | Aβ | Anti‐amyloid monoclonal antibody | NCT04451408 | Eli Lilly and Company | Jul 2020 | Jan 2024 |
| Mecamylamine | Sx, cognition | Neurotransmitter receptors | Nicotinic antagonist | NCT04129060 | University of Vermont | Mar 2020 | Mar 2024 |
| MK‐2214 | DMT, biologic | Tau | Anti‐tau monoclonal antibody | NCT05466422 | Merck Sharp & Dohme LLC | Sep 2022 | Nov 2024 |
| MK‐8189 | Sx, behavior | Neurotransmitter receptors | PDE10 inhibitor | NCT05227118 | Merck Sharp & Dohme LLC | Jul 2022 | Jan 2023 |
| Nicotinamide riboside | DMT, small molecule | Metabolism and bioenergetics | Mitochondrial function enhancer and antioxidant | NCT04430517 | Mclean Hospital | Mar 2022 | Apr 2025 |
| NIO752 | DMT, biologic | Other | Anti‐tau antisense oligonucleotide | NCT05469360 | Novartis Pharmaceuticals | Sep 2022 | Nov 2023 |
| Psilocybin | Sx, behavior | Neurotransmitter receptors | Psychedelic | NCT04123314 | Johns Hopkins University | Mar 2021 | Dec 2023 |
| Rapamycin | DMT, small molecule | Proteostasis/proteinopathies | Autophagy enhancer; mTOR inhibitor; immunomodulator | NCT04200911 | The University of Texas Health Science Center at San Antonio | Jun 2020 | Jan 2022 |
| Salsalate | DMT, small molecule | Inflammation | Non‐steroidal anti‐inflammatory (NSAID) | NCT03277573 | Adam Boxer | Jul 2017 | Apr 2021 |
| SHR‐1707 | DM, biologic | Aβ | Anti‐amyloid monoclonal antibody | NCT04973189 | Shanghai Hengrui Pharmaceutical Co., Ltd. | May 2021 | Oct 2021 |
| TB006 | DMT, biologic | Inflammation | Monoclonal antibody targeting galactose‐specific lectin (galectin) 3, a β‐galactosidase‐binding protein that activates macrophages; anti‐inflammatory | NCT04920786 | TrueBinding, Inc. | Jun 2021 | Nov 2022 |
| Tricaprilin | DMT, small molecule | Metabolism and bioenergetics | Caprylic triglyceride; induces ketosis to provide an alternate energy source to glucose and optimize mitochondrial function | NCT05028114 | Cerecin | Aug 2021 | Dec 2022 |
| NCT05408780 | Cerecin | Jul 2022 | Oct 2022 | ||||
| NCT05628636 | Cerecin | Nov 2022 | Feb 2023 | ||||
| VT301 | DMT, biologic | Inflammation | Regulatory T cells | NCT05016427 | VTBIO Co. LTD | Nov 2020 | Nov 2021 |
Abbreviations: Aβ, amyloid beta; APOE, apolipoprotein E; CADRO, Common Alzheimer's Disease Research Ontology; DMT, disease‐modifying therapy; mTOR, mammalian target or rapamycin; NCT#, National Clinical Trial number; Sx, symptoms.