TABLE 2.
Agents in Phase 2 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 |
|---|---|---|---|---|---|---|---|
| 50561 | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | RAC1 inhibitor (RAC family small GTPase inhibitors) enhance dendritic spine morphogenesis and synaptic plasticity | NCT05811442 | Beijing Joekai Biotechnology LLC | Apr 2023 | May 2024 |
| ABBV‐552 | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Synaptic vesicle glycoprotein 2A (SV2A) modulator | NCT05771428 | AbbVie | Apr 2023 | Jun 2024 |
| ABBV‐916 | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid antibody | NCT05291234 | AbbVie | Aug 2022 | Jan 2030 |
| ACI‐24.060 | Disease‐modifying biologic | Amyloid beta | Vaccine stimulates antibodies against amyloid beta protein | NCT05462106 | AC Immune SA | Jun 2022 | Jun 2026 |
| AL002 | Disease‐modifying biologic | Inflammation | Monoclonal antibody targeting TREM2 receptors | Alector Inc. |
Jan 2021 Jan 2023 |
Sep 2024 Sep 2025 |
|
| Allopregnanolone | Disease‐modifying small molecule | Neurogenesis | Allosteric modulator of GABA‐A Receptors | NCT04838301 | University of Arizona | Aug 2023 | Apr 2025 |
| ALZN002 | Disease‐modifying biologic | Amyloid beta | Autologous Beta‐Amyloid Mutant Peptide‐pulsed Dendritic Cells | NCT05834296 | Alzamend Neuro, Inc. | Jul 2023 | Mar 2028 |
| APH‐1105 | Disease‐modifying small molecule | Amyloid beta | Alpha‐secretase modulator (amyloid precursor protein secretase modulator) | NCT03806478 | Aphios | Jun 2023 | Sep 2024 |
| Astragalus | Cognitive enhancement | Inflammation | Undisclosed | NCT05647473 | Fujian Medical University Union Hospital | Feb 2024 | May 2025 |
| Bacillus Calmette‐Guerin | Disease‐modifying biologic | Inflammation | Vaccine to stimulate resilience to Alzheimer‐related processes | NCT05004688 | Steven E Arnold, MD | Mar 2022 | Oct 2023 |
| Baricitinib | Disease‐modifying small molecule | Inflammation | Janus kinase (JAK) inhibitor | NCT05189106 | Massachusetts General Hospital | Dec 2022 | Jul 2024 |
| Bepranemab | Disease‐modifying biologic | Tau | Anti‐tau monoclonal antibody binding to central region of tau | NCT04867616 | UCB Biopharma SRL | Jun 2021 | May 2024 |
| BIIB080 | Disease‐modifying biologic | Tau | Antisense oligonucleotide that inhibits translation of tau mRNA into the tau protein | NCT05399888 | Biogen | Aug 2022 | Nov 2027 |
| Brivaracetam | Cognitive enhancement | Neurotransmitter receptors | Anticonvulsant with high affinity for synaptic vesicle protein 2A | NCT05899764 | University of California, Los Angeles | Jun 2023 | Jun 2028 |
| Bumetanide | Disease‐modifying small molecule | ApoE, lipids and lipoprotein receptors | Reversal of ApoE‐specific AD signatures | NCT06052163 | Stanford University | Oct 2023 | Oct 2025 |
| Canakinumab | Disease‐modifying biologic | Inflammation | Anti‐IL‐1‐beta monoclonal antibody | NCT04795466 | Novartis Pharmaceuticals | Oct 2021 | Mar 2024 |
| Cannabidiol | Neuropsychiatric symptom | Neurotransmitter receptors | Endocannabinoid receptor agonist | NCT05822362 | University of Colorado, Denver | Jan 2024 | Apr 2028 |
| Chinese Traditional Medicine | Cognitive enhancement | 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 | Cognitive enhancement | Growth factors and hormones | Selective glucocorticoid receptor antagonist | NCT04601038 | Johns Hopkins University | Jun 2021 | Jun 2025 |
| CST‐2032 | Cognitive enhancement | Neurotransmitter receptors | Noradrenergic agonist | NCT05104463 | CuraSen Therapeutics, Inc. | Apr 2022 | Nov 2023 |
| CT1812 | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Sigma 2 receptor antagonist; binds to sigma‐2/PGRMC1 receptor and regulates Aβ oligomer‐mediated synaptic toxicity | Cognition Therapeutics |
Oct 2018 Jun 2023 |
Jul 2024 Apr 2027 |
|
| Dalzanemdor | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Enhnaces synaptic function through NMDA receptor blockade | NCT05619692 | Sage Therapeutics | Dec 2022 | Dec 2024 |
| Dasatinib + Quercetin | Disease‐modifying small molecule | Inflammation | Dasatinib induces apoptosis in senescent cells to allow their removal; quercetin is a flavonoid |
Wake Forest University Health Sciences James L. Kirkland, MD, PhD Lewis Lipsitz |
Dec 2021 Jul 2022 May 2022 |
Jan 2025 Dec 2023 Jun 2024 |
|
| Dexmedetomidine | Neuropsychiatric symptom | Neurotransmitter receptors | Presynaptic alpha‐2 adrenoceptor agonist to inhibit release of norepinephrine | NCT06052254 | Teikoku Pharma USA, Inc. | Dec 2023 | Dec 2024 |
| DHA | Disease‐modifying small molecule | Oxidative stress | Omega 3 fatty acid; reduce amyloid production; improve synaptic function; antioxidant | NCT03613844 | University of Southern California | Sep 2018 | May 2024 |
| Dronabinol | Neuropsychiatric symptom | Neurotransmitter receptors | CB1 and CB2 endocannabinoid receptor partial agonist | NCT02792257 | Johns Hopkins University | Mar 2017 | May 2024 |
| Dronabinol + PEA | Neuropsychiatric symptom | Neurotransmitter receptors | Cannibinoid | NCT05239390 | The Israeli Medical Center for Alzheimer's | Dec 2021 | Jun 2023 |
| E2814 | Disease‐modifying biologic | Tau | Anti‐tau monoclonal antibody | NCT04971733 | Eisai Inc. | Jun 2021 | Jul 2025 |
| Edaravone | Disease‐modifying small molecule | Oxidative stress | Pyrazolone free‐radical scavenger | NCT05323812 | Treeway B.V. | Mar 2023 | Jan 2024 |
| EX039 | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Inhibits D‐amino acids oxidate to increase N‐methyl‐D‐aspartate receptor activity | NCT05413655 | Excelsior | Aug 2022 | Aug 2025 |
| ExPlas | Disease‐modifying biologic | Synaptic plasticity/neuroprotection | Plasma transfusion from exercise‐trained donors | NCT05068830 | Norwegian University of Science and Technology | Sep 2021 | Sep 2024 |
| Flos gossypii flavonoids | Disease‐modifying small molecule | Oxidative stress | Antioxidant; anti‐inflammatory | NCT05269173 | Capital Medical University | Oct 2020 | Jun 2024 |
| GSK4527226 | Disease‐modifying biologic | Proteostasis/proteinopathies | Monoclonal antibody to sortilin (SORT1) to improve lysosomal function | NCT06079190 | GlaxoSmithKline | Oct 2023 | Dec 2026 |
| Hydroxypropyl beta‐cyclodextrin | Disease‐modifying 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 | Neuropsychiatric symptom | Neurotransmitter receptors | Cannabinoid | NCT05543681 | IGC Pharma LLC | Oct 2022 | Jun 2025 |
| Insulin | Disease‐modifying 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 | Disease‐modifying 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 |
| Interleukin‐2 | Disease‐modifying biologic | Inflammation | Restore function of regulatory T cells | NCT06096090 | The Methodist Hospital Research Institute | Mar 2023 | Dec 2025 |
| IVL3003 | Cognitive enhancement | Neurotransmitter receptors | Cholinesterase inhibitor | NCT05345509 | Inventage Lab., Inc. | Apr 2023 | Mar 2024 |
| JNJ‐63733657 | Disease‐modifying biologic | Tau | Monoclonal antibody targeted at soluble tau (mid‐region of tau) | NCT04619420 | Janssen Research & Development, LLC | Jan 2021 | Mar 2025 |
| JZP541 | Neuropsychiatric symptom | Neurotransmitter receptors | Cannabinoid receptor agonists of the endocannabinoid system | NCT06014424 | Sunnybrook Health Sciences Center | Sep 2023 | Dec 2026 |
| Lamivudine | Disease‐modifying small molecule | Epigenetic regulators | Human immunodeficiency virus nucleoside analog reverse transcriptase inhibitor | NCT04552795 | Bess Frost, PhD | Feb 2021 | May 2023 |
| Lecanemab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody directed at amyloid protofibrils and amyloid plaques | NCT01767311 | Eisai Inc. | Dec 2012 | Feb 2025 |
| Lenalidomide | Disease‐modifying small molecule | Inflammation | Anti‐inflammatory and immunomodulatory originally approved to treat multiple myeloma |
St. Joseph's Hospital and Medical Center, Phoenix |
Jul 2020 Jan 2024 |
Sep 2023 Jan 2026 |
|
| Leuprorelin | Disease‐modifying small molecule | Growth factors and hormones | Gonadotropin releasing hormone (GnRH) receptor agonist | NCT03649724 | Weill Medical College of Cornell University | Nov 2020 | Feb 2025 |
| Levetiracetam | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | SV2A modulator enhancing synaptic plasticity |
Beth Israel Deaconess Medical Center Walter Reed National Military Medical Center |
Aug 2019 Jan 2020 |
Aug 2023 Dec 2024 |
|
| L‐Serine | Disease‐modifying small molecule | Inflammation | Naturally‐occurring dietary amino acid; inhibits toxic misfolding | NCT03062449 | Aleksandra Stark | Mar 2017 | Dec 2022 |
| 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 | NCT03634007 | Lexeo Therapeutics | Nov 2019 | Nov 2024 |
| LY3372689 | Disease‐modifying small molecule | Tau | O‐GlcNAcase enzyme inhibitor | NCT05063539 | Eli Lilly and Company | Sep 2021 | Jul 2024 |
| Memantine | Disease‐modifying small molecule | Neurotransmitter receptors | NMDA receptor antagonist | NCT05063851 | University of Virginia | Oct 2021 | Dec 2025 |
| Methylene Blue | Disease‐modifying small molecule | Tau | Tau protein aggregation inhibitor | NCT02380573 | The University of Texas Health Science Center at San Antonio | Jul 2015 | Apr 2022 |
| MIB‐626 | Disease‐modifying small molecule | Amyloid beta | Sirtuin‐nicotinamide adenine dinucleotide stimulator to enhance alpha‐secretase | NCT05040321 | Brigham and Women's Hospital | Dec 2021 | Apr 2024 |
| Montelukast buccal film | Disease‐modifying small molecule | Inflammation | Leukotriene receptor antagonist (LTRA); anti‐inflammatory effects | NCT03402503 | IntelGenx Corp. | Nov 2018 | Feb 2024 |
| MW150 | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | p38 alpha MAPK kinase inhibitor | NCT05194163 | Neurokine Therapeutics | May 2022 | Aug 2024 |
| NanoLithium NP03 | Disease‐modifying small molecule | Neurotransmitter receptors | Ion with effects on amyloid, oxidation, and inflammation | NCT05423522 | Medesis Pharma SA | May 2022 | Jan 2024 |
| Nicotine transdermal patch | Cognitive enhancement | Neurotransmitter receptors | Nicotinic acetylcholine receptor agonist | NCT02720445 | University of Southern California | Jan 2017 | Aug 2025 |
| Pegipanermin | Disease‐modifying biologic | Inflammation | Neutralizes TNF‐alpha |
Inmune Bio, Inc. |
Feb 2022 Feb 2023 |
Dec 2024 May 2026 |
|
| Pepinemab | Disease‐modifying biologic | Inflammation | Monoclonal antibody directed at semaphorin 4D; reduces inflammatory cytokine release | NCT04381468 | Vaccinex Inc. | Jul 2021 | Jun 2023 |
| PRI‐002 | Disease‐modifying small molecule | Amyloid beta | Interferes with oligomerization of A‐beta 42 to prevent formation and enhance reduction of A‐beta oligomers | NCT06182085 | PRInnovation GmbH | Dec 2023 | Apr 2026 |
| PrimeC | Disease‐modifying small molecule | Inflammation | Combined product targeting inflammation, iron accumulation, impaired RNA regulation | NCT06185543 | NeuroSense Therapeutics Ltd. | Nov 2023 | Nov 2025 |
| Proleukin | Disease‐modifying biologic | Inflammation | IL‐2 immunomodulator | NCT05468073 | Center Hospitalier St Anne | Oct 2022 | Sep 2025 |
| Rapamycin | Disease‐modifying small molecule | Proteostasis/proteinopathies | Autophagy enhancer; MTOR inhibitor; immunomodulator |
The University of Texas Health Science Center at San Antonio Karolinska Institutet |
Aug 2021 Sep 2023 |
Dec 2023 Jan 2025 |
|
| REM0046127 | Cognitive enhancement | Neurotransmitter receptors | Modulates Orai calcium (Ca2+) channel activity to normalize neuronal Ca2+ homeostasis | NCT05478031 | reMYND | Jun 2022 | Jun 2023 |
| Sargramostim | Disease‐modifying biologic | Inflammation | Hematopoietic growth factor granulocyte macrophage colony stimulating factor; anti‐inflammatory | NCT04902703 | University of Colorado, Denver | Jun 2022 | Jul 2024 |
| Seltorexant | Neuropsychiatric symptom | Circadian rhythm | Dual orexin receptor antagonist | NCT05307692 | Janssen Research & Development, LLC | May 2022 | Oct 2023 |
| Senicapoc | Disease‐modifying small molecule | Inflammation | Calcium‐activated potassium channel inhibitor | NCT04804241 | University of California, Davis | Mar 2022 | Dec 2024 |
| Simufilam | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Filamin A conformation stabilizer; disrupts the interaction of filamin A with the alpha 7 nicotinic acetylcholine receptor to reduce tau hyperphosphorylation and neurodegeneration; dependent on A‐beta's signaling via the alpha 7 pathway | NCT05352763 | Cassava Sciences, Inc. | May 2022 | Oct 2025 |
| Suvorexant | Disease‐modifying small molecule | Neurotransmitter receptors | Dual orexin receptor antagonist | NCT04629547 | Washington University School of Medicine | May 2022 | May 2026 |
| TB006 | Disease‐modifying biologic | Inflammation | Monoclonal antibody targeting galactose‐specific lectin (galectin) 3, a β‐galactosidase‐binding protein that activates macrophages; anti‐inflammatory | NCT05476783 | TrueBinding, Inc. | Sep 2022 | Oct 2024 |
| Tdap | Disease‐modifying 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 | Disease‐modifying small molecule | Vasculature | Angiotensin II receptor blocker | NCT02085265 | Sunnybrook Health Sciences Center | Mar 2014 | Sep 2023 |
| Tertomotide | Disease‐modifying biologic | Synaptic plasticity/neuroprotection | Human telomerase reverse transcriptase (hTERT) mimic | NCT05189210 | GemVax & Kael | Oct 2022 | Jul 2023 |
| THC‐free cannabidiol | Neuropsychiatric symptom | Neurotransmitter receptors | Cannabinoid | NCT04436081 | Eastern Virginia Medical School | Feb 2021 | Mar 2024 |
| Trazodone | Cognitive enhancement | Circadian rhythm | Serotonin reuptake inhibitor | NCT05282550 | Johns Hopkins University | Jan 2023 | Mar 2027 |
| Trontinemab | Disease‐modifying biologic | Amyloid beta | Monoclonal antibody directed at plaques and oligomers; “brain‐shuttle” gantenerumab | NCT04639050 | Hoffmann‐La Roche | Mar 2021 | Sep 2027 |
| Valacyclovir | Disease‐modifying small molecule | Inflammation | Anti‐viral against HSV‐1 and −2; reduces vira‐related ‘seeding’ of amyloid plaque deposition | NCT03282916 | Columbia University | Feb 2018 | Dec 2024 |
| Valiltramiprosate | Disease‐modifying small molecule | Amyloid beta | Aggregation Inhibitor | NCT04693520 | Alzheon Inc. | Sep 2020 | Jul 2023 |
| Varoglutamstat | Disease‐modifying small molecule | Amyloid beta | Glutaminyl cyclase (QC) enzyme inhibitor to reduce production of pyroglutamate Aβ | Vivoryon Therapeutics N.V. |
Nov 2021 Jul 2020 |
Nov 2023 Jan 2024 |
|
| Wei Li Bai | Disease‐modifying small molecule | Metabolism and bioenergetics | Not specified; reported to regulate metabolism, improve blood circulation, and exert anti‐inflammatory and antioxidant effects | NCT05670912 | Capital Medical University | Oct 2022 | Nov 2024 |
| Xanamem | Cognitive enhancement | Growth factors and hormones | 11‐beta‐hydroxysteroid dehydrogenase type 1 inhibitor | NCT06125951 | Actinogen Medical | Dec 2023 | Dec 2025 |
| Yangxue Qingnao pills | Disease‐modifying small molecule | Vasculature | Cerebral blood flow enhancer; traditional Chinese herbal medicine | NCT04780399 | Dongzhimen Hospital, Beijing | Nov 2021 | Mar 2024 |