Intervention Sponsors & Collaborators Phase Type of Therapy Path To

Data Table Complete Report is Available from AlzDiscovery.org *Intervention received support from the ADDF

Sponsors & Secondary Other Names | Intervention Collaborators Phase Type of Therapy Path to Clinic Primary Target Target Relevant Links Mechanism of Action

Axon Neuroscience https://ClinicalTrials.gov/sh AC-AD-003 | Axon peptide AADvac1 SE Phase 2 Biologic Novel Misfolded Proteins Tau ow/NCT02579252 108 conjugated to KLH https://ClinicalTrials.gov/sh ABBV-8E12 AbbVie Phase 2 Biologic Novel Misfolded Proteins Tau ow/NCT02880956

https://www.clinicaltrialsregi ster.eu/ctr-search/trial/2016- Abvac40 Araclon Biotech Phase 2 Biologic Novel Misfolded Proteins Amyloid 004352-30/ES Phase 2 | Mitochondria & https://ClinicalTrials.gov/sh AC-1204 Accera, Inc. Phase 3 Natural Product Other Metabolic Function ow/NCT01741194 Ketogenic

https://www.clinicaltrialsregi ster.eu/ctr-search/trial/2008- ACI-24 AC Immune SA Phase 2 Biologic Novel Misfolded Proteins Amyloid 006257-40/DK Pal1-15 acetate salt http://www.acimmune.com/ AC Immune SA | en/ad-treatment-and- ACI-35 Janssen Phase 1 Biologic Novel Misfolded Proteins Tau prevention/#aci-35 Ageless Adipose Derived Stromal Regenerative Phase 1 | https://clinicaltrials.gov/ct2/ Autologous Adipose- Cells Institute Phase 2 Cell Therapy Novel Neuroprotection show/NCT02912169 Derived Stromal Cells https://ClinicalTrials.gov/sh ow/NCT02484547 BIIB037 | Microglial- https://clinicaltrials.gov/sho mediated phagocytosis and Aducanumab Biogen Phase 3 Biologic Novel Misfolded Proteins Amyloid w/NCT02477800 clearance of amyloid Low-dose levetiracetam | Phase 2 Synaptic Activity & https://clinicaltrials.gov/ct2/ Pre-synaptic calcium AGB101 * Agenebio, Inc. completed Small Molecule Repurposed Neurotransmitters show/NCT01044758 channel inhibitor Intravenous Instituto Grifols, S.A. | Immunoglobulin, Human Grifols Biologicals Phase 2 | https://ClinicalTrials.gov/sh Albumin Combined With Albumin | Immune globulin Inc. Phase 3 Biologic Repurposed Misfolded Proteins Amyloid ow/NCT01561053 Flebogamma University of 3α,5α- Southern California | Neuronal tetrahydroprogesterone, 3α- National Institute on Phase 1 Regeneration & https://ClinicalTrials.gov/sh hydroxy-5α-pregnan-20- Allopregnanolone * Aging (NIA) completed Biologic Other Neuroprotection Repair ow/NCT02221622 one Tramiprosate | Amyloid aggregation inhibitor, activity at GABA synapse https://alzheon.com/underly (unclear if agonist or ALZ-801 Alzheon Phase 1 Small Molecule Other Misfolded Proteins Amyloid ing-clinical-data/ antagonist)

AZTherapies, Inc. | PharmaConsulting Group | KCAS Bio | Repurposed Neuroinflammati https://ClinicalTrials.gov/sh Cromolyn sodium, ALZT-OP1 APCER Life Sciences Phase 3 Small Molecule (Combination Therapy) Inflammation on ow/NCT02547818 Ibuprofen

Sigma1/muscarinic receptor binder, Anavex Life Sciences https://clinicaltrials.gov/sho intracellular sigma-1 ANAVEX2-73 Corp. Phase 2 Small Molecule Novel Neuroprotection w/NCT02756858 chaperone protein agonist Phase 1 | https://ClinicalTrials.gov/sh AstroStem Nature Cell Co. Ltd. Phase 2 Cell Therapy Novel Neuroprotection ow/NCT03117738 Autologous fat stem cells Emory University | National Institute on Synaptic Activity & https://ClinicalTrials.gov/sh ATX-001 | Norepinephrine Atomoxetine * Aging (NIA) Phase 2 Small Molecule Repurposed Neurotransmitters ow/NCT01522404 reuptake inhibitor Yale University | Saracatinib | Kinase Alzheimer's Inhibitor; Src tyrosine Therapeutic Neurodegenerati https://clinicaltrials.gov/sho kinase inhibitor (NCATS AZD0530 Research Insititute Phase 2 Small Molecule Repositioned Neuroprotection on w/NCT02167256 molecule) https://ClinicalTrials.gov/sh Neuroinflammati ow/NCT02916056 F-04494700, TTP488 | Azeliragon vTv Therapeutics Phase 3 Small Molecule Novel Inflammation on NCT02080364 RAGE inhibitor

Charsire https://ClinicalTrials.gov/sh Biotechnology Corp. | ow/NCT02467413 BAC-01, BAC-02 | A2 Healthcare https://clinicaltrials.gov/sho Bacterial artificial BAC Taiwan Corporation Phase 2 Unknown Unknown Unknown w/NCT02886494 chromosome (BAC) https://ClinicalTrials.gov/sh BAN2401 Eisai Inc. | Biogen Phase 2 Biologic Novel Misfolded Proteins Amyloid ow/NCT01767311 Burke Medical Research Institute | Burke Rehabilitation Hospital | Columbia University | National Institute on Aging (NIA) | Alzheimer's BRC-451, 1R01AG043679- Drug Discovery Mitochondria & https://ClinicalTrials.gov/sh 01A1 | Vitamin B1 type Benfotiamine * Foundation Phase 2 Small Molecule Repurposed Metabolic Function ow/NCT02292238 antioxidant https://clinicaltrials.gov/sho w/NCT02240693 https://clinicaltrials.gov/sho w/NCT02337907 Synaptic Activity & https://clinicaltrials.gov/sho Phosphodiesterase 9A BI 409306 Boehringer Ingelheim Phase 2 Small Molecule Novel Neurotransmitters w/NCT02392468 inhibitor https://ClinicalTrials.gov/sh Anti-tau monoclonal BIIB076 Biogen Phase 1 Biologic Novel Misfolded Proteins Tau ow/NCT03056729 antibody

National Institute on Aging (NIA) | National Institutes of Health Synaptic Activity & https://ClinicalTrials.gov/sh Butyrylcholinesterase Bisnorcymserine (BNC ) Clinical Center (CC) Phase 1 Small Molecule Novel Neurotransmitters ow/NCT01747213 inhibitor https://ClinicalTrials.gov/sh ow/NCT02840279 Negative allosteric Tetra Discovery Phase 1 Synaptic Activity & https://clinicaltrials.gov/sho modulator of BPN14770 * Partners completed Small Molecule Novel Neurotransmitters w/NCT02648672 phosphodiesterase 4D Neuronal Neurotrope Regeneration & https://ClinicalTrials.gov/sh Bryostatin 1 * Bioscience, Inc. Phase 2 Small Molecule Other Neuroprotection Repair ow/NCT02431468 Protein kinase C modulator https://ClinicalTrials.gov/sh Angiotensin receptor Candesartan * Emory University Phase 2 Small Molecule Repurposed Vascular ow/NCT02646982 blocker Phase 1 | https://ClinicalTrials.gov/sh CB-AC-02 CHABiotech CO., Ltd Phase 2 Cell Therapy Novel Neuroprotection ow/NCT02899091 Placenta derived-MSCs National Cerebral Vasodilator, and Cardiovascular https://clinicaltrials.gov/ct2/ phosphodiesterase 3 Cilostazol Center, Japan Phase 2 Small Molecule Repurposed Vascular show/NCT02491268 antagonist Novartis Pharmaceuticals | Amgen | Banner Alzheimer's Phase 2 | https://ClinicalTrials.gov/sh CNP520 Institute|Novartis Phase 3 Small Molecule Novel Misfolded Proteins Amyloid ow/NCT03131453 BACE1 inhibitor Novartis Pharmaceuticals | Banner Alzheimer's Institute | National Institute on Aging (NIA) | Alzheimer's Phase 2 | Small Molecule + Novel (Combination https://ClinicalTrials.gov/sh Amyloid antibody, BACE1 CNP520 | CAD106 Association | Amgen Phase 3 Biologic Therapy) Misfolded Proteins Amyloid ow/NCT02565511 inhibitor

https://clinicaltrials.gov/sho Combination of Donepezil Chase w/NCT02549196 (an acetylcholinesterase Pharmaceuticals Small Molecule + Novel + Donepezil Synaptic Activity & https://clinicaltrials.gov/sho inhibitor) with a peripherally CPC-201 Corporation Phase 2 Biologic (Combination Therapy) Neurotransmitters w/NCT02860065 acting cholinergic blocker https://ClinicalTrials.gov/sh Hoffmann-La Roche | ow/NCT02670083 MABT5102A, RG7412 | Genentech | AC Phase 2 | NCT01998841 Amyloid phagocytosis Crenezumab Immune Phase 3 Biologic Novel Misfolded Proteins Amyloid NCT03114657 stimulator Phase 2 Neuroinflammati https://clinicaltrials.gov/ct2/ CHF 5074 | Microglia 'M2' CSP-1103 CereSpir completed Small Molecule Novel Inflammation on show/NCT01303744 inducer Cognition Phase 1 | Neurodegenerati https://ClinicalTrials.gov/sh Sigma2/PGRMC1 receptor CT1812 * Therapeutics Phase 2 Small Molecule Novel Neuroprotection on ow/NCT02907567 binder

Combination of Donepezil (an acetylcholinesterase inhibitor) with AMPA Daehwa receptor modulator, MAPK Pharmaceutical Co., Novel + Donepezil Synaptic Activity & https://clinicaltrials.gov/ct2/ modulator, protein kinase DHP1401 | Donepezil Ltd. Phase 2 Small Molecule (Combination Therapy) Neurotransmitters show/NCT03055741 modulator Synaptic Activity & https://clinicaltrials.gov/ct2/ Phosphodiesterase 9A E2027 Eisai Inc. Phase 1 Small Molecule Novel Neurotransmitters show/NCT02873156 (PDE9) inhibitor https://ClinicalTrials.gov/sh ow/NCT02322021 NCT03036280 Phase 2 | https://clinicaltrials.gov/sho Elenbecestat | BACE1 E2609 Eisai Inc. | Biogen Phase 3 Small Molecule Novel Misfolded Proteins Amyloid w/NCT02956486 inhibitor

https://www.clinicaltrialsregi University of Systemic ster.eu/ctr-search/trial/2015-Enbrel ™ | TNF-alpha Etanercept * Southampton Phase 2 Small Molecule Repurposed Inflammation Inflammation 002145-63/GB inhibitor

National Institute on https://ClinicalTrials.gov/sh Aging (NIA) | National ow/NCT01255163 Exenatide, Byetta, Institutes of Health Phase 2 Mitochondria & https://clinicaltrials.gov/ct2/ Bydureon | GLP-1 receptor Exendin-4 Clinical Center (CC) completed Small Molecule Repurposed Metabolic Function show/NCT02847403 agonist Palo Alto Veterans Institute for Research | Alzheimer's Association|Mylan Synaptic Activity & https://ClinicalTrials.gov/sh β-2 adrenergic receptor Formoterol Inc. Phase 2 Small Molecule Repurposed Neurotransmitters ow/NCT02500784 agonist https://ClinicalTrials.gov/sh ow/NCT01224106 https://clinicaltrials.gov/sho Gantenerumab Hoffmann-La Roche Phase 3 Biologic Novel Misfolded Proteins Amyloid w/NCT02051608 RO4909832, RG1450 Washington University School of Medicine | Eli Lilly and Company | Hoffmann-La Roche | Alzheimer's Association | National Institute on Aging (NIA) | Avid Radiopharmaceutical s | Accelerating Gantenerumab | Medicines Phase 2 | Novel (Combination https://ClinicalTrials.gov/sh Solanezumab Partnership (AMP) Phase 3 Biologic Therapy) Misfolded Proteins Amyloid ow/NCT01760005 Phase 1 Neuroinflammati https://ClinicalTrials.gov/sh GC021109 * GliaCure, Inc. completed Small Molecule Novel Inflammation on ow/NCT02386306 P2Y6 agonist Gregory Jicha | University of https://ClinicalTrials.gov/sh Micro-RNA pathways Gemfibrozil Kentucky Phase 1 Small Molecule Repurposed Vascular ow/NCT02045056 modulator Johns Hopkins University | Icahn Grape Seed Polyphenolic School of Medicine at Other (Combination Mitochondria & https://clinicaltrials.gov/ct2/ Extract | Resveratrol Mount Sinai Phase 1 Natural Product Therapy) Metabolic Function show/NCT02502253 Imperial College Synaptic Activity & https://ClinicalTrials.gov/sh Noradrenergic add-on Guanfacine London Phase 3 Small Molecule Repurposed Neurotransmitters ow/NCT03116126 therapy Telomerase vaccine, cellular proliferation inducer, anti-apoptotic effects, mitochondrial https://ClinicalTrials.gov/sh stabilizer, anti-aging and GV1001 GemVax & Kael Phase 2 Biologic Repurposed Neuroprotection Oxidative Stress ow/NCT03184467 antioxidant effects

Heptares Therapeutics Limited Synaptic Activity & https://ClinicalTrials.gov/sh Muscarinic M1 receptor HTL0009936 | P1vital Limited Phase 1 Small Molecule Novel Neurotransmitters ow/NCT02546310 agonist VA Office of Research and Eicosapentaenoic acid, Development | CLNA-001-15S, CX001261 University of Phase 2 | https://ClinicalTrials.gov/sh | Derivative of omega-3 Icosapent ethyl (IPE) Wisconsin, Madison Phase 3 Small Molecule Other Vascular ow/NCT02719327 fatty acid

University of Southern California | National Institute on Aging (NIA) | Alzheimer's Therapeutic Research Institute (ATRI) | Wake Forest Phase 2 | Mitochondria & https://ClinicalTrials.gov/sh Insulin (Humulin R U-100) * School of Medicine Phase 3 Biologic Repurposed Metabolic Function ow/NCT01767909 Wake Forest School of Medicine | National Institute on Aging (NIA) | General Mitochondria & https://ClinicalTrials.gov/sh Detemir, Levemir, Humulin, Insulin aspart Electric Phase 1 Biologic Repurposed Metabolic Function ow/NCT02462161 Novolin Wake Forest School of Medicine | Alzheimer's Mitochondria & https://ClinicalTrials.gov/sh Increases insulin signaling Insulin detemir Association Phase 2 Biologic Repurposed Metabolic Function ow/NCT01595646 in the brain

HealthPartners Institute for Education Mitochondria & https://ClinicalTrials.gov/sh Increases insulin signaling Insulin glulisine and Research Phase 2 Biologic Repurposed Metabolic Function ow/NCT02503501 in the brain

Ionis Phase 1 | https://ClinicalTrials.gov/sh ISIS 814907-CS1 | IONIS MAPTRx Pharmaceuticals, Inc. Phase 2 Biologic Novel Misfolded Proteins Tau ow/NCT03186989 Antisense oligonucleotide https://ClinicalTrials.gov/sh Janssen Research & ow/NCT02569398 Development, LLC | Phase 2 | https://clinicaltrials.gov/sho JNJ-54861911 Shionogi Pharma Phase 3 Small Molecule Novel Misfolded Proteins Amyloid w/NCT02406027 BACE Inhibitor https://clinicaltrials.gov/sho w/NCT02127476 Kyowa Hakko Kirin https://ClinicalTrials.gov/sh KHK6640 Company, Limited Phase 1 Biologic Novel Misfolded Proteins Amyloid ow/NCT02377713

Dartmouth-Hitchcock Medical Center | Brain Chemistry Laboratories, Institute https://ClinicalTrials.gov/sh L-Serine for Ethnomedicine Phase 2 Natural Product Other Neuroprotection ow/NCT03062449 Non-essential amino acid https://ClinicalTrials.gov/sh ow/NCT02245737 https://clinicaltrials.gov/sho w/NCT02783573 Eli Lilly and Company https://clinicaltrials.gov/sho LY3314814, AZD3293 | Lanabecestat | AstraZeneca Phase 3 Small Molecule Novel Misfolded Proteins Amyloid w/NCT02972658 BACE inhibitor University of California, San Synaptic Activity & https://ClinicalTrials.gov/sh Pre-synaptic calcium Levetiracetam Francisco Phase 2 Small Molecule Repurposed Neurotransmitters ow/NCT02002819 channel inhibitor

Imperial College London | King's College Hospital NHS Trust | University of Oxford | University of Southampton | Avon and Wiltshire Mental Health Partnership Mitochondria & https://ClinicalTrials.gov/sh Liraglutide * NHS Trust Phase 2 Small Molecule Repurposed Metabolic Function ow/NCT01843075 GLP-1 receptor agonist

https://ClinicalTrials.gov/sh ow/NCT03069014 https://www.clinicaltrialsregi Phase 1 | Growth/Neurotro ster.eu/ctr-search/trial/2015- LM11A-31 * PharmatrophiX Phase 2 Small Molecule Novel Neuroprotection phic Factors 005263-16/AT H. Lundbeck A/S | Otsuka Phase 3 Synaptic Activity & https://clinicaltrials.gov/sho Idalopirdine | 5-HT6 Lu AE58054 Pharmaceutical completed Small Molecule Novel Neurotransmitters w/NCT02006654 receptor antagonist H. Lundbeck A/S | Otsuka Novel (Combination Synaptic Activity & https://ClinicalTrials.gov/sh Idalopirdine | 5-HT6 Lu AE58054 | Memantine Pharmaceutical Phase 3 Small Molecule Therapy) Neurotransmitters ow/NCT02079246 receptor antagonist https://ClinicalTrials.gov/sh Lu AF20513 H. Lundbeck A/S Phase 1 Biologic Novel Misfolded Proteins Amyloid ow/NCT02388152 https://ClinicalTrials.gov/sh ow/NCT02624778 https://ClinicalTrials.gov/sh N3pG-Aβ monoclonal LY3002813 Eli Lilly and Company Phase 1 Biologic Novel Misfolded Proteins Amyloid ow/NCT01837641 antibody https://ClinicalTrials.gov/sh LY3202626 Eli Lilly and Company Phase 2 Small Molecule Novel Misfolded Proteins Amyloid ow/NCT02791191 BACE inhibitor https://ClinicalTrials.gov/sh LY3303560 Eli Lilly and Company Phase 1 Biologic Novel Misfolded Proteins Tau ow/NCT02754830 Tau antibody Phase 3 Neuroinflammati https://ClinicalTrials.gov/sh Masitinib AB Science completed Small Molecule Repurposed Inflammation on ow/NCT01872598 Tyrosine kinase inhibitor AstraZeneca | Eli Lilly Phase 1 https://ClinicalTrials.gov/sh MEDI1814 and Company completed Biologic Novel Misfolded Proteins Amyloid ow/NCT02036645 Monomeric amyloid binder Hillel Grossman, Icahn School of Medicine at Mount Sinai | National Center for Complementary and Meganatural-Az Grapeseed Integrative Health https://clinicaltrials.gov/ct2/ Extract (NCCIH) Phase 2 Natural Product Other Misfolded Proteins Amyloid show/NCT02033941 Anti-oligomerization agent Longeveron LLC | Stemedica Cell https://ClinicalTrials.gov/sh Technologies, Inc. | ow/NCT02600130 Allogeneic Human Mesenchymal Stem Cells Stemedica Phase 1 | https://clinicaltrials.gov/sho Mesenchymal Stem Cell (Allogeneic) International SA Phase 2 Cell Therapy Novel Neuroprotection w/NCT02833792 Infusion South China Research Center for Stem Cell and Regenerative Medicine | Third Affiliated Hospital, Sun Yat-Sen https://ClinicalTrials.gov/sh University | Sun Yat- ow/NCT02672306 Sen Memorial https://clinicaltrials.gov/sho Hospital of Sun Yat- w/NCT02513706 Sen University | https://clinicaltrials.gov/sho Guangzhou w/NCT02054208 Human Umbilical Cord- Mesenchymal Stem Cells Psychiatric Hospital | Phase 1 | https://ClinicalTrials.gov/sh Derived Mesenchymal (Umbilical Cord) Medipost Co Ltd. Phase 2 Cell Therapy Novel Neuroprotection ow/NCT03172117 Stem Cells

Peter Fox | Texas Alzheimer's Research and Care Consortium (TARCC) | The University of Texas Health Science Center at San https://ClinicalTrials.gov/sh Methylene Blue Antonio Phase 2 Small Molecule Repurposed Misfolded Proteins Proteostasis ow/NCT02380573

https://www.clinicaltrialsregi King's College Neuroinflammati ster.eu/ctr-search/trial/2013- Minocycline London Phase 2 Small Molecule Repurposed Inflammation on 000397-30/GB Acnamino Neuronal National University Regeneration & https://ClinicalTrials.gov/sh MLC901 Hospital, Singapore Phase 2 Natural Product Other Neuroprotection Repair ow/NCT03038035 Neuroaid II Metabolic Solutions D evelopment Compan Phase 2 Mitochondria & https://clinicaltrials.gov/ct2/ Mitoglitazone | mTOT MSDC-0160 * y completed Small Molecule Novel Metabolic Function show/NCT01374438 modulator https://ClinicalTrials.gov/sh NewGam 10% IVIG Sutter Health Phase 2 Biologic Other Misfolded Proteins Amyloid ow/NCT01300728 NeuroGenetic Pharmaceuticals Inc | Phase 1 https://ClinicalTrials.gov/sh Gamma-secretase NGP 555 WCCT Global completed Small Molecule Novel Misfolded Proteins Amyloid ow/NCT02537938 modulator University of Mitochondria & https://ClinicalTrials.gov/sh Nicotinamide California, Irvine Phase 2 Natural Product Other Metabolic Function ow/NCT03061474 Vitamin B3

University of Southern California | National Institute on Aging (NIA) | Vanderbilt University | Alzheimer's Therapeutic Synaptic Activity & https://ClinicalTrials.gov/sh Nicotinic acetylcholine Nicotine Transdermal Patch * Research Institute Phase 2 Natural Product Other Neurotransmitters ow/NCT02720445 receptor agonist

Georgetown https://clinicaltrials.gov/sho Tasinga® | Tyrosine kinase Nilotinib * University Phase 2 Small Molecule Repurposed Misfolded Proteins Proteostasis w/NCT02947893 inhibitor, c-abl inhibitor University of Dublin, Trinity College | Molecular Medicine Ireland LBG | Alzheimer Europe | Archer Pharmaceuticals, Inc. | E-Search Limited | University College Dublin | GABO:mi | King's College London | Istituto Di Ricerche Farmacologiche Mario Negri | University Hospital, Lille | University of Ulm | Szeged University | Goeteborgs Universitet | University College Cork | Aristotle University Of Thessaloniki | Stichting Katholieke Phase 3 https://clinicaltrials.gov/ct2/ Nilvad, Nivadil, ARC029 | Nilvadipine * Universiteit completed Small Molecule Repurposed Vascular show/NCT02017340 Calcium channel blocker Stabilized, pH adjusted sodium chlorite | Immune Neuraltus Systemic https://clinicaltrials.gov/ct2/ regulator of inflammatory NP001 Pharmaceuticals, Inc. Phase 1 Small Molecule Novel Inflammation Inflammation show/NCT03179501 monocytes/macrophages

Proclara Biosciences, Fusion protein combining Inc. | Alzheimer's https://ClinicalTrials.gov/sh GAIM with the backbone of NPT088 Association Phase 1 Biologic Novel Misfolded Proteins Amyloid, Tau ow/NCT03008161 a human immunoglobulin Oregon Health and Science University | National Institute on https://clinicaltrials.gov/ct2/ Omega-3 polyunsaturated Omega-3 PUFA Aging (NIA) Phase 2 Natural Product Other Vascular show/NCT01953705 fatty acids, fish oil

https://www.oryzon.com/en/ news/oryzon-presents-final- data-phase-i-trial-ory-2001- Genetics & alzheimer%E2%80%99s- ORY-2001 * Oryzon Genomics Phase 1 Small Molecule Novel Epigenetics Epigenetics association-international LSD1/MOA-B inhibitor Russell Swerdlow, MD | University of Kansas Medical Mitochondria & https://ClinicalTrials.gov/sh Oxaloacetate (OAA) Center Phase 1 Natural Product Other Metabolic Function ow/NCT02593318 Phase 1 https://clinicaltrials.gov/ct2/ Casein kinase I PF-05251749 Pfizer completed Small Molecule Novel Unknown show/NCT02691702 delta/epsilon Phase 1 https://clinicaltrials.gov/ct2/ Gamma-secretase PF-06648671 Pfizer completed Small Molecule Novel Misfolded Proteins Amyloid show/NCT02407353 modulator Phase 1 https://clinicaltrials.gov/sho Speculation this is an PF-06751979 Pfizer completed Small Molecule Novel Unknown w/NCT02793232 enzyme inhibitor

Takeda https://ClinicalTrials.gov/sh Pharmaceutical ow/NCT01931566 Company | Zinfandel Mitochondria & https://ClinicalTrials.gov/sh AD4833, Actos®, Pioglitazone Pharmaceuticals Inc. Phase 3 Small Molecule Repurposed Metabolic Function ow/NCT02284906 Glustin™, Piozone® Neu-P11 | Melatonin MT₁/MT₂ and serotonin 5- Neurim Synaptic Activity & https://ClinicalTrials.gov/sh HT1A/5-HT1D receptor Piromelatine Pharmaceuticals Ltd. Phase 2 Small Molecule Repositioned Neurotransmitters ow/NCT02615002 agonist Stanford University | Systemic https://clinicaltrials.gov/ct2/ Plasma Alkahest, Inc. Phase 1 Biologic Other Inflammation Inflammation show/NCT02256306

QR Pharma Inc. | Alzheimer's Disease QR15001, ADC-042-DISC Cooperative Study Phase 1 | Amyloid, Tau, https://ClinicalTrials.gov/sh | Selective inhibitor of APP Posiphen (ADCS) Phase 2 Small Molecule Novel Misfolded Proteins Synuclein ow/NCT02925650 production Probiodrug AG | Glutaminyl-peptide Julius Clinical | VU cyclotransferase inhibitor, University Medical Phase 2 https://ClinicalTrials.gov/sh targeting pyroglutamate PQ912 Center Amsterdam completed Small Molecule Novel Misfolded Proteins Amyloid ow/NCT02389413 amyloid (pGlu-Abeta) Douglas Mental Health University Institute | Weston Anti-hyperlipidemic, Brain Institute | McGill Phase 1 | Genetics & https://clinicaltrials.gov/ct2/ promotes ApoE availability Probucol University Phase 2 Small Molecule Repurposed Epigenetics ApoE show/NCT02707458 in CSF

Combination of Pharnext SA | acamprosate Ca2+ (analog Ascopharm Groupe Phase 2 Repurposed Synaptic Activity & https://clinicaltrials.gov/ct2/ of GABA) and baclofin PXT00864 Novasco completed Small Molecule (Combination Therapy) Neurotransmitters show/NCT02361242 (GABA-B activator) https://ClinicalTrials.gov/sh (MAO-B) Monoamine Rasagiline * The Cleveland Clinic Phase 2 Small Molecule Repurposed Neuroprotection ow/NCT02359552 oxidase B inhibitor

Protects against glutamate Synaptic Activity & https://ClinicalTrials.gov/sh excitotoxicity, recovers Riluzole * Rockefeller University Phase 2 Small Molecule Repurposed Neurotransmitters ow/NCT01703117 EAAT2 gene expression Phase 1 https://ClinicalTrials.gov/sh RO 7105705 Genentech, Inc. completed Biologic Novel Misfolded Proteins Tau ow/NCT02820896 RG 6100 Santa Lucia Synaptic Activity & Rotigotine * Foundation Phase 2 Small Molecule Repurposed Neurotransmitters Dopaminergic therapy https://ClinicalTrials.gov/sh ow/NCT02586909 https://clinicaltrials.gov/sho w/NCT02910102 Axovant Sciences Phase 2 | Synaptic Activity & https://clinicaltrials.gov/sho Intepirdine | 5-HT6 RVT-101 Ltd. Phase 3 Small Molecule Novel Neurotransmitters w/NCT02585934 receptor antagonist Russell Swerdlow, MD | Ausio Pharmaceuticals, LLC | University of Kansas Medical Phase 1 | https://clinicaltrials.gov/sho Estrogen receptor β (ERβ) S -Equol Center Phase 2 Natural Product Other Neuroprotection w/NCT03101085 agonist Monoclonal antibody, Phase 1 https://clinicaltrials.gov/ct2/ amyloid fibrillogenesis SAR228810 Sanofi completed Biologic Novel Misfolded Proteins Amyloid show/NCT01485302 inhibitor GM-CSF, Leukine | University of Granulocyte colony Colorado, Denver | Systemic https://ClinicalTrials.gov/sh stimulator, promotes Sargramostim * The Dana Foundation Phase 2 Biologic Repurposed Inflammation Inflammation ow/NCT01409915 amyloid clearance University of Wisconsin, Madison | National Institute on https://clinicaltrials.gov/ct2/ HMG-CoA reductase Simvastatin Aging (NIA) Phase 2 Small Molecule Repurposed Vascular show/NCT00939822 inhibitor (statin) University of Combination of HMG-CoA Simvastatin + L-Arginine + Massachusetts, Small Molecule + Repurposed + Other https://ClinicalTrials.gov/sh reductase inhibitor and Tetrahydrobiopterin Worcester Phase 2 Natural Product (Combination Therapy) Vascular ow/NCT01439555 antioxidant Shanghai Greenvalley GV-971 | Amyloid Pharmaceutical Co., https://ClinicalTrials.gov/sh aggregation inhibitor, Sodium oligo-mannurarate Ltd. Phase 3 Small Molecule Novel Misfolded Proteins Amyloid ow/NCT02293915 reduces AChE activity

Sinphar Repurposed + Antioxidant properties of Pharmaceutical Co., Donepezil https://clinicaltrials.gov/sho echinascoside, anti- STA-1 | Donezepil Ltd Phase 2 Small Molecule (Combination Therapy) Neuroprotection Oxidative Stress w/NCT01255046 inflammatory https://ClinicalTrials.gov/sh CTP2S1502HT6 | Suven Life Sciences Synaptic Activity & ow/NCT02580305 Selective 5-HT6 receptor SUVN-502 Limited Phase 2 Small Molecule Novel Neurotransmitters antagonist

Toyama Chemical Co., Ltd. | Alzheimer's Disease Cooperative Study Phase 2 https://ClinicalTrials.gov/sh Neurotrophic agent, sigma T-817 MA (ADCS) completed Small Molecule Novel Neuroprotection ow/NCT02079909 receptor agonist PPARdelta/gamma agonist (PPAR activation boosts insulin sensitivity and T3D Therapeutics, Phase 1 | Mitochondria & https://ClinicalTrials.gov/sh regulates triglyceride T3D-959 Inc. Phase 2 Small Molecule Novel Metabolic Function ow/NCT02560753 levels)

St. George's, University of London| Alzheimer’s Drug Discovery Foundation | Alzheimer's Society UK | University of Copenhagen | University of Glasgow | St George's University Hospitals NHS Foundation https://clinicaltrials.gov/ct2/ Tadalafil * Trust Phase 2 Small Molecule Repurposed Vascular show/NCT02450253 CIALIS® | PDE5 inhibitor Muscarinic M1 receptor Novel + Donepezil Synaptic Activity & https://ClinicalTrials.gov/sh positive allosteric TAK-071 | Donepezil Takeda Phase 1 Small Molecule (Combination Therapy) Neurotransmitters ow/NCT02769065 modulator https://ClinicalTrials.gov/sh Angiotensin 2 receptor Telmisartan Emory University Phase 1 Small Molecule Repurposed Vascular ow/NCT02471833 antagonist

Dr. Sandra E Black | Comparative effectiveness Alzheimer's Drug study of angiotensin 2 Discovery Foundation receptor antagonist | Sunnybrook Health https://ClinicalTrials.gov/sh (Telmisartan) and ACE Telmisartan | Perindopril * Sciences Centre Phase 2 Small Molecule Repurposed Vascular ow/NCT02085265 inhibitor (Perindopril) University of Next generation taxane | California, San https://ClinicalTrials.gov/sh Microtubule stabilizer, TPI-287 Francisco Phase 1 Small Molecule Novel Misfolded Proteins Tau ow/NCT01966666 tubulin-binding

LMTM and LMT-X, purified form of methylene blue | TauRx Therapeutics https://ClinicalTrials.gov/sh Tau aggregation inhibitor TRx0237 Ltd Phase 3 Small Molecule Repurposed Misfolded Proteins Tau ow/NCT02245568 (or potentially dissolver) United Neuroscience https://clinicaltrials.gov/sho UB-311 Ltd. Phase 2 Biologic Novel Misfolded Proteins Amyloid w/NCT02551809 Synthetic peptide vaccine Prodrug of acyclovir | Anti- viral, herpes virus Hugo Lovheim | Systemic https://ClinicalTrials.gov/sh nucleoside analog DNA Valaciclovir Umeå University Phase 2 Small Molecule Repurposed Inflammation Inflammation ow/NCT02997982 polymerase inhibitor Merck Sharp & https://clinicaltrials.gov/sho Verubecestat Dohme Corp. Phase 3 Small Molecule Novel Misfolded Proteins Amyloid w/NCT01953601 MK-8931 | BACE1 inhibitor German Center for Neurodegenerative Diseases (DZNE) | University Hospital, N-hydroxy-N'-phenyl- Bonn | University of Genetics & https://ClinicalTrials.gov/sh octanediamide | HDAC Vorinostat Göttingen Phase 1 Small Molecule Repurposed Epigenetics Epigenetics ow/NCT03056495 inhibitor, antineoplastic

Vanderbilt University | Vanderbilt University Synaptic Activity & https://clinicaltrials.gov/ct2/ VU0467319 | M1 Positive VU319 * Medical Center Phase 1 Small Molecule Novel Neurotransmitters show/NCT03220295 Allosteric Modulator Neflamapomid | P38 mitogen-activated protein kinase inhibitor (inhibits the Phase 2 Neuroinflammati https://clinicaltrials.gov/sho alpha isoform of p38 VX-745 EIP Pharma, LLC completed Small Molecule Repurposed Inflammation on w/NCT02423200 MAPK) Actinogen Medical | ICON Clinical https://clinicaltrials.gov/sho 11-HSD1 enzyme activity Xanamem Research Phase 2 Small Molecule Novel Neuroprotection w/NCT02727699 inhibitor