TABLE 3.
Agents in Phase 1 Alzheimer's disease drug development (clinicaltrials.gov accessed January 1, 2024).
| Agent | Therapeutic purpose | CADRO target | Mechanism of action | Clinical trial | Lead sponsor | Start date | Estimated primary completion date |
|---|---|---|---|---|---|---|---|
| Allopregnanolone | Disease‐modifying small molecule | Neurogenesis | Allosteric modulator of GABA‐A Receptors | NCT03748303 | University of Arizona | Oct 2019 | Dec 2022 |
| ALN‐APP | Disease‐modifying biologic | Amyloid beta | RNAi to decrease APP and downstream Aβ‐related events | NCT05231785 | Alnylam Pharmaceuticals | Feb 2022 | Jul 2025 |
| ALZ‐101 | Disease‐modifying biologic | Amyloid beta | Amyloid beta‐directed vaccine | NCT05328115 | Alzinova AB | Sep 2021 | Dec 2023 |
| APNmAb005 | Disease‐modifying biologic | Tau | Anti‐tau antibody | NCT05344989 | APRINOIA Therapeutics, LLC | May 2022 | Mar 2024 |
| AV‐1959 | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid vaccine | NCT05642429 | Institute for Molecular Medicine | Feb 2023 | Feb 2026 |
| Bacillus Calmette‐Guerin | Disease‐modifying biologic | Inflammation | Vaccine to stimulate resilience to Alzheimer‐related processes | NCT06078891 | Tamir Ben‐Hur | Jul 2023 | Jul 2024 |
| BMS‐984923 | Disease‐modifying small molecule | Amyloid beta | Silent allosteric modulator (SAM) of mGluR5 | Allyx Therapeutics |
Mar 2023 Jan 2023 |
Oct 2024 Feb 2023 |
|
| Cannabidiol | Neuropsychiatric symptom | Neurotransmitter Receptors | Cannabinoid | NCT04075435 | Mclean Hospital | Jan 2021 | Sep 2024 |
| Centella asiatica product | Disease‐modifying small molecule | Synaptic Plasticity/Neuroprotection | Antioxidant and anti‐inflammatory agent with synaptic and neuroprotective effects | NCT05591027 | Oregon Health and Science University | Dec 2022 | Nov 2024 |
| Choline | Disease‐modifying small molecule | Metabolism and Bioenergetics | Stabilizes the lipid metabolism and concomitantly restoring normal cell function by increasing phosphatidylcholine activity via the Kennedy pathway | NCT05880849 | Paul E Schulz | Jun 2023 | Jun 2025 |
| CpG1018 | Disease‐modifying biologic | Inflammation | Toll‐like receptor nine agonist leading to reduced Aβ plaques and tau pathology | NCT05606341 | NYU Langone Health | Mar 2023 | Nov 2024 |
| CS6253 | Disease‐modifying biologic | ApoE, Lipids and Lipoprotein Receptors | Adenosine triphosphate‐binding cassette transporter A1 (ABCA1) transfers lipids to ApoE, and increases clearance of A‐beta from the brain | NCT05965414 | Artery Therapeutics, Inc. | Oct 2023 | Sep 2024 |
| Donepezil | Cognitive enhancement | Neurotransmitter Receptors | Cholinesterase inhibitor | NCT06127368 | G2GBio, Inc. | Jan 2024 | Sep 2024 |
| Emtricitabine | Disease‐modifying small molecule | Inflammation | Nucleoside reverse transcriptase inhibitor (NRTI) | NCT04500847 | Butler Hospital | Dec 2021 | Mar 2024 |
| IBC‐Ab002 | Disease‐modifying biologic | Inflammation | Anti‐programmed death‐ligand 1 (PD‐L1) immune checkpoint inhibitor | NCT05551741 | Immunobrain Checkpoint | Feb 2023 | Oct 2024 |
| LX1001 | Disease‐modifying biologic | ApoE, Lipids and Lipoprotein Receptors | Adeno‐associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2) directly to the CNS/CSF of APOE4 homozygotes | NCT05400330 | Lexeo Therapeutics | May 2023 | Nov 2028 |
| Mecamylamine | Cognitive enhancement | Neurotransmitter Receptors | Nicotinic antagonist | NCT04129060 | University of Vermont | Mar 2020 | Mar 2024 |
| MK‐2214 | Disease‐modifying biologic | Tau | Anti‐tau monoclonal antibody | NCT05466422 | Merck Sharp & Dohme LLC | Sep 2022 | May 2025 |
| Nicotinamide Riboside | Disease‐modifying small molecule | Metabolism and Bioenergetics | Mitochondrial function enhancer and antioxidant | NCT04430517 | Mclean Hospital | Mar 2022 | Apr 2025 |
| NIO752 | Disease‐modifying biologic | Tau | Anti‐tau antisense oligonucleotide | NCT05469360 | Novartis Pharmaceuticals | Feb 2023 | Oct 2024 |
| OLX‐07010 | Disease‐modifying small molecule | Tau | Inhibits tau self‐aggregation | NCT05696483 | Oligomerix, Inc | Jan 2023 | Dec 2024 |
| Probiotic Blend Capsule | Disease‐modifying small molecule | Gut‐Brain Axis | Inflammation/immunity | NCT06181513 | University of Nicosia | Dec 2022 | Jul 2024 |
| Psilocybin | Neuropsychiatric symptom | Neurotransmitter Receptors | Psychedelic | NCT04123314 | Johns Hopkins University | Mar 2021 | Dec 2024 |
| Remternetug | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody | NCT04451408 | Eli Lilly and Company | Jul 2020 | Aug 2024 |
| SHR‐1707 | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody | NCT06114745 | Atridia Pty Ltd. | Jan 2024 | Nov 2025 |