TABLE 2.
Agents in Phase 2 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 |
|---|---|---|---|---|---|---|---|
| ABBV‐916 | DMT, biologic | Aβ | Anti‐amyloid antibody | NCT05291234 | AbbVie | Aug 2022 | Dec 2024 |
| ABvac40 | DMT, biologic | Aβ | Active immunotherapy (SC injection) | NCT03461276 | Araclon Biotech S.L. | Feb 2018 | Dec 2021 |
| ACI‐24.060 | DMT, biologic | Aβ | Vaccine stimulates antibodies against Aβ protein | NCT05462106 | AC Immune SA | Jun 2022 | Jun 2026 |
| ACI‐35 | DMT, biologic | Tau | Active immunotherapy targeting tau (phosphorylated tau) | NCT04445831 | AC Immune SA | Jul 2019 | Oct 2023 |
| AL 001 | DMT, small molecule | Synaptic plasticity/neuroprotection | Lithium inhibits GSL3‐beta activating mTOR to facilitate the Akt signaling pathway | NCT05363293 | Alzamend Neuro, Inc. | May 2022 | Dec 2022 |
| AL002 | DMT, biologic | Inflammation | Monoclonal antibody targeting TREM2 receptors | NCT04592874 | Alector Inc. | Jan 2021 | Dec 2023 |
| Allopregnanolone | DMT, small molecule | Neurogenesis | Allosteric modulator of GABA‐A receptors | NCT04838301 | University of Arizona | Jan 2023 | Jan 2025 |
| APH‐1105 | DMT, small molecule | Aβ | Alpha secretase modulator (amyloid precursor protein secretase modulator) | NCT03806478 | Aphios | Jun 2023 | Sep 2024 |
| Bacillus Calmette‐Guerin | DMT, biologic | Inflammation | Immunomodulation | NCT05004688 | Steven E. Arnold | Mar 2022 | Oct 2023 |
| Baricitinib | DMT, small molecule | Inflammation | Janus kinase (JAK) inhibitor | NCT05189106 | Massachusetts General Hospital | Dec 2022 | Jul 2024 |
| Bepranemab | DMT, biologic | Tau | Anti‐tau monoclonal antibody binding to central region of tau | NCT04867616 | UCB Biopharma SRL | Jun 2021 | Apr 2024 |
| BIIB080 | DMT, biologic | Tau | Antisense oligonucleotide that inhibits translation of tau mRNA into the tau protein | NCT05399888 | Biogen | Aug 2022 | Dec 2026 |
| Brain shuttle gantenerumab | DMT, biologic | Aβ | Monoclonal antibody directed at plaques and oligomers; "brain‐shuttle" gantenerumab | NCT04639050 | Hoffmann‐La Roche | Mar 2021 | Jan 2025 |
| Bryostatin 1 | DMT, biologic | Synaptic plasticity/neuroprotection | Protein kinase C inhibitor | NCT04538066 | Neurotrope Bioscience, Inc. | Aug 2020 | Nov 2022 |
| Buntanetap | DMT, small molecule | Proteostasis/proteinopathies | Reduce amyloid precursor protein (APP) synthesis; selective inhibitor of APP to reduce amyloid; reduces synthesis of tau and alpha‐synuclein proteins | NCT02925650 | Annovis Bio Inc. | Mar 2017 | Dec 2021 |
| Canakinumab | DMT, biologic | Inflammation | Anti‐IL‐1‐beta monoclonal antibody | NCT04795466 | Novartis Pharmaceuticals | Oct 2021 | Feb 2026 |
| Chinese traditional medicine | Sx, cognition | Metabolism and bioenergetics | Three herbs (Rhizoma Acori Tatarinowii, Poria cum Radix Pini, Radix Polygalae) mechanism unknown | NCT05538507 | Peking Union Medical College Hospital | Jun 2022 | Jun 2024 |
| CORT108297 | Sx, cognition | Growth factors and hormones | Selective glucocorticoid receptor antagonist | NCT04601038 | Johns Hopkins University | Jun 2021 | Jun 2023 |
| Crenezumab | DMT, biologic | Aβ | Monoclonal antibody targeting soluble oligomers | NCT01998841 | Genentech, Inc. | Dec 2013 | Mar 2022 |
| CST‐2032 | Sx, cognition | Neurotransmitter receptors | Noradrenergic agonist | NCT05104463 | CuraSen Therapeutics, Inc. | Apr 2022 | Jun 2023 |
| CY6463 | DMT, small molecule | Synaptic plasticity/neuroprotection | Guanylate cyclase positive allosteric modulator | NCT04798989 | Cyclerion Therapeutics | Jun 2021 | Jul 2022 |
| Dalzanemdor | DMT, small molecule | Synaptic plasticity/neuroprotection | Enhances synaptic function through NMDA receptor blockade | NCT05619692 | Sage Therapeutics | Feb 2023 | Dec 2024 |
| Dapagliflozin | DMT, small molecule | Metabolism and bioenergetics | Sodium‐glucose cotransporter 2 (SGLT2) Inhibitor | NCT03801642 | Jeff Burns, MD | Jan 2019 | Oct 2022 |
| Daratumumab | DMT, biologic | Inflammation | Human antibody targeting CD38; immunomodulatory effects | NCT04070378 | Marc L. Gordon, MD | Nov 2019 | Dec 2023 |
| Dasatinib + quercetin | DMT, small molecule | Inflammation | Dasatinib induces apoptosis in senescent cells to allow their removal; quercetin is a flavonoid | NCT04063124 | The University of Texas Health Science Center at San Antonio | Feb 2020 | Dec 2021 |
| NCT04685590 | Wake Forest University Health Sciences | Dec 2021 | Jan 2027 | ||||
| NCT04785300 | James L. Kirkland, MD, PhD | Jul 2022 | Dec 2023 | ||||
| NCT05422885 | Lew Lipsitz | May 2022 | Jun 2023 | ||||
| Deferiprone | DMT, small molecule | Cell death | Iron chelating agent | NCT03234686 | Neuroscience Trials Australia | Jan 2018 | Sep 2022 |
| DHA | DMT, small molecule | Oxidative stress | Omega 3 fatty acid; reduce amyloid production; improve synaptic function; antioxidant | NCT03613844 | University of Southern California | Jul 2018 | May 2024 |
| Dronabinol | Sx, behavior | Neurotransmitter receptors | CB1 and CB2 endocannabinoid receptor partial agonist | NCT02792257 | Johns Hopkins University | Mar 2017 | May 2023 |
| E2814 | DMT, biologic | Tau | Anti‐tau monoclonal antibody | NCT04971733 | Eisai Inc. | Jun 2021 | Sep 2024 |
| Edaravone | DMT, small molecule | Oxidative stress | Pyrazolone free‐radical scavenger | NCT05323812 | Treeway B.V. | Sep 2022 | Jan 2024 |
| Edonerpic | DMT, small molecule | Synaptic plasticity/neuroprotection | Neurotrophic agent; activates sigma‐1 receptor; enhances microglial clearance of Aβ | NCT04191486 | FUJIFILM Toyama Chemical Co., Ltd. | Dec 2019 | Feb 2023 |
| Elayta | DMT, small molecule | Synaptic plasticity/neuroprotection | Sigma 2 receptor antagonist; binds to sigma‐2/PGRMC1 receptor and regulates Aβ oligomer‐mediated synaptic toxicity | NCT03507790 | Cognition Therapeutics | Oct 2018 | Sep 2023 |
| NCT04735536 | Cognition Therapeutics | Aug 2020 | Mar 2023 | ||||
| NCT05531656 | Cognition Therapeutics | Dec 2022 | Aug 2026 | ||||
| EX039 | DMT, small molecule | Synaptic plasticity/neuroprotection | Inhibits D‐amino acids oxidate to increase NMDA receptor activity | NCT05413655 | Excelsior | Aug 2022 | Aug 2024 |
| ExPlas | DMT, biologic | Synaptic plasticity/neuroprotection | Plasma transfusion from exercise‐trained donors | NCT05068830 | Norwegian University of Science and Technology | Sep 2021 | Sep 2024 |
| Flos gossypii flavonoids | DMT, small molecule | Oxidative stress | Anti‐oxidant; anti‐inflammatory | NCT05269173 | Capital Medical University | Oct 2020 | Jun 2024 |
| Fosgonimeton (ATH‐1017) | DMT, small molecule | Synaptic plasticity/neuroprotection | Hepatocyte growth factor (HGF); activates signaling via the HGF/MET receptor system; promotes survival of neurons, enhances hippocampal synaptic plasticity | NCT04886063 | Athira Pharma | Jun 2021 | Apr 2023 |
| Gantenerumab | DMT, biologic | Aβ | Monoclonal antibody directed at plaques and oligomers | NCT04592341 | Hoffmann‐La Roche | Nov 2020 | Dec 2022 |
| GnRH | DMT, biologic | Growth factors and hormones | Antiaging | NCT04390646 | Nelly Pitteloud | Aug 2020 | Dec 2023 |
| Hydroxypropyl Beta Cyclodextrin | DMT, biologic | apoE, lipids, and lipoprotein receptors | Modulates cholesterol transportation with secondary effects on amyloid, tau, and oxidative e stress | NCT05607615 | Cyclo Therapeutics, Inc. | Sep 2022 | Mar 2024 |
| IGC‐AD1 | Sx, behavior | Neurotransmitter receptors | Cannabinoid | NCT05543681 | IGC Pharma LLC | Oct 2022 | Aug 2023 |
| Insulin | DMT, biologic | Metabolism and bioenergetics | Decreases glucose resistance; increase insulin signaling in the brain | NCT05006599 | Wake Forest University Health Sciences | May 2025 | May 2029 |
| Insulin + empagliflozin | DMT, biologic | Metabolism and bioenergetics | SGLT2 inhibitor (empagliflozin) and insulin combination therapy; decrease glucose resistance and increase insulin signaling in the brain | NCT05081219 | Wake Forest University Health Sciences | Oct 2021 | Oct 2026 |
| IVL3003 | Sx, cognition | Neurotransmitter receptors | Cholinesterase inhibitor | NCT05345509 | Inventage Lab., Inc. | Apr 2023 | Mar 2024 |
| JNJ‐63733657 | DMT, biologic | Tau | Monoclonal antibody targeted at soluble tau (mid‐region of tau) | NCT04619420 | Janssen Research & Development, LLC | Jan 2021 | Mar 2025 |
| L‐Serine | DMT, small molecule | Inflammation | Naturally occurring dietary amino acid; inhibits toxic misfolding | NCT03062449 | Aleksandra Stark | Mar 2017 | Dec 2022 |
| Lamivudine | DMT, small molecule | Epigenetic regulators | Human immunodeficiency virus nucleoside analog reverse transcriptase inhibitor | NCT04552795 | Bess Frost, PhD | Feb 2021 | Mar 2023 |
| Lecanemab | DMT, biologic | Aβ | Anti‐amyloid monoclonal antibody directed at amyloid protofibrils and amyloid plaques | NCT01767311 | Eisai Inc. | Dec 2012 | Feb 2025 |
| Lenalidomide | DMT, small molecule | Inflammation | Immunomodulator | NCT04032626 | St. Joseph's Hospital and Medical Center, Phoenix | Jul 2020 | Sep 2023 |
| Leuprorelin | DMT, small molecule | Growth factors and hormones | Gonadotropin releasing hormone (GnRH) receptor agonist | NCT03649724 | Weill Medical College of Cornell University | Nov 2020 | Feb 2025 |
| Levetiracetam | DMT, small molecule | Synaptic plasticity/neuroprotection | SV2A modulator enhancing synaptic plasticity | NCT03489044 | University of Oxford | Oct 2018 | Dec 2022 |
| NCT03875638 | Beth Israel Deaconess Medical Center | Aug 2019 | Aug 2023 | ||||
| NCT04004702 | Walter Reed National Military Medical Center | Jan 2020 | Dec 2024 | ||||
| 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 | NCT03634007 | Lexeo Therapeutics | Nov 2019 | Apr 2023 |
| LY3372689 | DMT, small molecule | Tau | O‐GlcNAcase enzyme inhibitor | NCT05063539 | Eli Lilly and Company | Sep 2021 | May 2024 |
| Memantine | DMT, small molecule | Neurotransmitter receptors | NMDA receptor antagonist | NCT05063851 | University of Virginia | Oct 2021 | Sep 2024 |
| Methylene Blue | DMT, small molecule | Tau | Tau protein aggregation inhibitor | NCT02380573 | The University of Texas Health Science Center at San Antonio | Jul 2015 | Apr 2022 |
| MIB‐626 | DMT, small molecule | Aβ | Sirtuin‐nicotinamide adenine dinucleotide stimulator to enhance alpha‐secretase | NCT05040321 | Brigham and Women's Hospital | Dec 2021 | Feb 2024 |
| MK‐1942 | Sx, cognition | Neurotransmitter receptors | Undisclosed | NCT05602727 | Merck Sharp & Dohme LLC | Dec 2022 | May 2026 |
| Montelukast | DMT, small molecule | Inflammation | Leukotriene receptor antagonist (LTRA); anti‐inflammatory effects | NCT03402503 | IntelGenx Corp. | Nov 2018 | Oct 2023 |
| MW150 | DMT, small molecule | Synaptic plasticity/neuroprotection | p38 alpha MAPK kinase inhibitor | NCT05194163 | Neurokine Therapeutics | May 2022 | Aug 2024 |
| NanoLithium NP03 | DMT, small molecule | Neurotransmitter receptors | Ion with effects on amyloid, oxidation, and inflammation | NCT05423522 | Medesis Pharma SA | May 2022 | May 2023 |
| Neflamapimod | DMT, small molecule | Synaptic plasticity/neuroprotection | Selective p38 MAPK alpha inhibitor | NCT03435861 | University Hospital, Toulouse | Oct 2018 | Apr 2021 |
| Nicotine | Sx, cognition | Neurotransmitter receptors | Nicotinic acetylcholine receptor agonist | NCT02720445 | University of Southern California | Jan 2017 | Jul 2023 |
| Obicetrapib | DMT, small molecule | apoE, lipids, and lipoprotein receptors | Cholesteryl ester transfer protein (CETP) inhibitor | NCT05161715 | NewAmsterdam Pharma | Jan 2022 | Jun 2023 |
| Pegipanermin | DMT, biologic | Inflammation | Neutralizes TNF‐alpha | NCT05318976 | Inmune Bio, Inc. | Feb 2022 | Jun 2023 |
| NCT05321498 | Inmune Bio, Inc. | Sep 2022 | Jan 2023 | ||||
| NCT05522387 | Inmune Bio, Inc. | Nov 2022 | Dec 2025 | ||||
| Pepinemab | DMT, biologic | Inflammation | Monoclonal antibody directed at semaphorin 4D; reduces inflammatory cytokine release | NCT04381468 | Vaccinex Inc. | Jul 2021 | Dec 2023 |
| Proleukin | DMT, biologic | Inflammation | IL‐2 immunomodulator | NCT05468073 | Centre Hospitalier St Anne | Oct 2022 | Sep 2025 |
| Rapamycin | DMT, small molecule | Proteostasis/proteinopathies | Autophagy enhancer; mTOR inhibitor; immunomodulator | NCT04629495 | The University of Texas Health Science Center at San Antonio | Aug 2021 | Dec 2023 |
| REM0046127 | Sx, cognition | Neurotransmitter receptors | Modulates Orai calcium (Ca2+) channel activity to normalize neuronal Ca2+ homeostasis | NCT05478031 | reMYND | Jun 2022 | Jun 2023 |
| Sargramostim | DMT, biologic | Inflammation | Hematopoietic growth factor granulocyte macrophage colony stimulating factor; anti‐inflammatory | NCT04902703 | University of Colorado, Denver | Jun 2022 | Jul 2024 |
| SCI‐110 (Dronabinol + PEA) | Sx, behavior | Neurotransmitter receptors | Cannibinoid and palmitoylethanolamide (an endocannabinoid) | NCT05239390 | The Israeli Medical Center for Alzheimer's | Dec 2021 | Jun 2023 |
| Seltorexant | Sx, behavior | Circadian rhythm | Dual orexin receptor antagonist | NCT05307692 | Janssen Research & Development, LLC | May 2022 | Apr 2023 |
| Semorinemab | DMT, biologic | Tau | Anti‐tau monoclonal antibody targeting extracellular tau | NCT03828747 | Genentech, Inc. | Jan 2019 | Jul 2021 |
| Senicapoc | DMT, small molecule | Inflammation | Calcium‐activated potassium channel inhibitor | NCT04804241 | University of California, Davis | Mar 2022 | Dec 2024 |
| Simufilam | DMT, small molecule | Synaptic plasticity/neuroprotection | Filamin A protein inhibitor; stabilizes the interaction of Aβ42 and the α7 nicotinic acetylcholine receptor to decrease tau phosphorylation and improve synaptic function | NCT04388254 | Cassava Sciences, Inc. | Mar 2020 | Jan 2023 |
| NCT05352763 | Cassava Sciences, Inc. | May 2022 | Oct 2025 | ||||
| Sovateltide | DMT, small molecule | Neurogenesis | Endothelin B receptor agonist; augments activity of neuronal progenitor cells, neurovascular repair, and neuroregeneration | NCT04052737 | Pharmazz, Inc. | Mar 2018 | Nov 2022 |
| Suvorexant | DMT, small molecule | Neurotransmitter receptors | Dual orexin receptor antagonist | NCT04629547 | Washington University School of Medicine | May 2022 | May 2026 |
| T3D‐959 | DMT, small molecule | Metabolism and bioenergetics | Dual agonist of peroxisome proliferator activated nuclear receptor delta/gamma (PPARδ/γ); regulates glucose and lipid metabolism | NCT04251182 | T3D Therapeutics, Inc. | Mar 2021 | Apr 2023 |
| TB006 | DMT, biologic | Inflammation | Monoclonal antibody targeting galactose‐specific lectin (galectin) 3, a β‐galactosidase‐binding protein that activates macrophages; anti‐inflammatory | NCT05074498 | TrueBinding, Inc. | Oct 2021 | Oct 2022 |
| NCT05476783 | TrueBinding, Inc. | Sep 2022 | Oct 2024 | ||||
| Tdap | DMT, biologic | Inflammation | Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine to stimulate inflammatory protection | NCT05183516 | Mindful Diagnostics and Therapeutics, LLC | May 2023 | Dec 2023 |
| Telmisartan + perindopril | DMT, small molecule | Vasculature | Angiotensin II receptor blocker, PPAR‐gamma agonist (telmisartan); angiotensin converting enzyme inhibitor (perindopril) | NCT02085265 | Sunnybrook Health Sciences Centre | Mar 2014 | Sep 2023 |
| Tertomotide | DMT, biologic | Synaptic plasticity/neuroprotection | Human telomerase reverse transcriptase (hTERT) mimic | NCT05189210 | GemVax & Kael | Oct 2022 | Jul 2023 |
| THC‐free cannabidiol | Sx, behavior | Neurotransmitter receptors | Cannabinoids | NCT04436081 | Eastern Virginia Medical School | Feb 2021 | Dec 2022 |
| Trazodone | Sx, cognition | Circadian rhythm | Serotonin reuptake inhibitor | NCT05282550 | Johns Hopkins University | Jan 2023 | Mar 2027 |
| Trehalose injection | DMT, small molecule | Proteostasis/proteinopathies | Activates transcription factor EB to increase autophagy | NCT05332678 | Neuroscience Trials Australia | Jan 2023 | Jan 2025 |
| Valacyclovir | DMT, small molecule | Inflammation | Anti‐viral against HSV‐1 and −2; reduces vira‐related “seeding” of amyloid plaque deposition | NCT03282916 | New York State Psychiatric Institute | Feb 2018 | Dec 2023 |
| Valiltramiprosate (ALZ‐801) | DMT, small molecule | Aβ | Aggregation inhibitor | NCT04693520 | Alzheon Inc. | Sep 2020 | Jul 2023 |
| Varoglutamstat | DMT, small molecule | Aβ | Glutaminyl cyclase (QC) enzyme inhibitor to reduce production of pyroglutamate Aβ | NCT03919162 | Vivoryon Therapeutics N.V. | Nov 2021 | May 2023 |
| NCT04498650 | Vivoryon Therapeutics N.V. | Jul 2020 | Jan 2024 | ||||
| Yangxue Qingnao pills | DMT, small molecule | Vasculature | Cerebral blood flow enhancer; traditional Chinese herbal medicine | NCT04780399 | Dongzhimen Hospital, Beijing | Nov 2021 | Mar 2024 |
Abbreviations: Aβ, amyloid beta; Akt, protein kinase B; APOE, apolipoprotein E; CADRO, Common Alzheimer's Disease Research Ontology; CNS, central nervous system; CSF, cerebrospinal fluid; DMT, disease‐modifying therapy; HSV, herpes simplex virus; IL, interleukin; MAPK, mitogen‐activated protein kinase; mTOR, mammalian target or rapamycin; NCT#, National Clinical Trial number; NMDA, N‐methyl‐D‐aspartic acid; PPAR, peroxisome proliferator‐activated receptor; SC, subcutaneous; Sx, symptoms; TNF, tumor necrosis factor.