Alzheimer's Disease (Phase I - II) Drug Development Phase Organisations Drug Introduction Synonyms Mechanism Of Action Indication Phase Route Country Name Role Country Type Ownership Immune globulin 10% - Octapharma has developed an intravenously 10% high purity immunoglobulin Immunostimulants Immunodeficiency disorders Marketed IV Europe Octapharma Originator Switzerland Company Octapharma administered human normal immunoglobulin (10% concentration) for use in disorders of the immune system. The product was launched in Europe in 2008 under the brand name octagam® 10% for several indications.

Octagam® 10% has been launched as 10% IVIG Immunodeficiency disorders Phase III IV USA Octapharma Owner Switzerland Company 1 replacement therapy for primary immunodeficiency syndromes such as: primary humoral immunodeficiency (PI); [CONT.]

NewGam Alzheimer's disease (In the elderly) Phase II IV USA NewGam™ octagam 10% octagam immunoglobulin 10% octagam® 10% octagam® 10% EVP 6124 EnVivo Pharmaceuticals is developing the orally EVP-6124 Alpha7 nicotinic acetylcholine receptor agonists Cognition disorders Phase III PO USA Bayer HealthCare Originator Germany Pharmaceutical Public administered, selective alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) agonist, EVP 6124, for the treatment of Alzheimer's disease and cognition disorders. Improved cholinergic function is known to reduce cognitive 2 deficits in patients with Alzheimer's disease, and a selective alpha7-nAChR agonist may enhance cognition without causing the adverse events associated with overactivation of other nAChRs or MT-4666 Alzheimer's disease Phase II PO Japan, Romania, Russia, Serbia, Ukraine, USA Bayer HealthCare Owner Germany Pharmaceutical Public muscarinic acetylcholine receptors [CONT.] Cognition disorders Phase II PO Russia, Serbia, Ukraine EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private Mitsubishi Tanabe Pharma Corporation Licensee Asia Large Pharma, Pharmaceutical Public Davunetide intranasal Davunetide is an eight-amino acid peptide (i.e. AL 108 Microtubule-associated protein modulators Progressive supranuclear palsy II/III Intranasal Australia, Canada, France, Germany, United Kingdom, USA Allon Therapeutics Licensee Canada Biotechnology Public Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from an (Fast Track) endogenous brain neuroprotective protein, called activity-dependent neuroprotective protein (ADNP). Allon Therapeutics (a subsidiary of Paladin Labs) is developing an intranasal 3 formulation of davunetide (AL 108) for the treatment of mild cognitive impairment (MCI) related to schizophrenia, Alzheimer's disease AL-108 Tau protein inhibitors Alzheimer's disease Phase II Intranasal USA National Institutes of Health (USA) Originator USA Institution N/A (AD), Parkinson's disease (PD) and progressive AL108 Tubulin polymerisation promoters Mild cognitive impairment Phase II Intranasal USA Tel Aviv University Originator Israel University N/A supranuclear palsy (PSP; a type of NAP Schizophrenia Phase II Intranasal USA frontotemporal dementia) [CONT.] NAPVSIPQ Parkinson's disease Preclinical Intranasal USA ABT 126 AbbVie is developing ABT 126, an alpha 7 ABT-126 Nicotinic receptor antagonists Alzheimer's disease Phase II PO Bulgaria, Canada, Czech Republic, France, Germany, Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public neuronal nicotinic receptor (alpha7 NNR) Greece, Poland, Russia, Slovakia, South Africa, Ukraine, antagonist, as an orally administered treatment United Kingdom, USA for Alzheimer's disease and cognition disorders in patients with schizophrenia. Phase II 4 development for Alzheimer's disease is underway in the US, Canada, South Africa and certain European countries. Phase II development is Cognition disorders Phase II PO USA AbbVie Owner USA Biopharmaceutical Public underway in the US for cognition disorders in Alzheimer's disease (Combination therapy) Phase I PO USA patients with schizophrenia. [CONT.] Alzheimer's disease (In the elderly, In volunteers) Phase I PO USA ABT 288 AbbVie (formerly Abbott Laboratories) is ABT-288 Neurotransmitter receptor modulators Alzheimer's disease Phase II PO Russia, Ukraine Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public developing ABT 288 as a potential treatment for Alzheimer's disease and schizophrenia. A phase II 5 trial in the treatment of Alzheimer's disease has been completed in Russia and the Ukraine, and a phase II trial in the treatment of schizophrenia has been conducted in the US. [CONT.] Schizophrenia Phase II PO USA AbbVie Owner USA Biopharmaceutical Public ABT 384 AbbVie (formerly Abbott Laboratories) is ABT-384 Undefined mechanism Alzheimer's disease Phase II PO Russia, South Africa, Ukraine, United Kingdom Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public developing ABT 384 as a potential therapy for the treatment of neurological disorders. A phase II trial in patients with mild-to-moderate 6 Alzheimer's disease has been completed in Russia, South Africa, Ukraine and the UK. It appears that this therapy is being developed for oral administration. [CONT.] Neurological disorders (In volunteers) Phase I Unknown route USA AbbVie Owner USA Biopharmaceutical Public ACI 91 AC Immune is developing an oral formulation of ACI-91 BACE1 protein inhibitors Alzheimer's disease Phase II PO Switzerland AC Immune Originator Switzerland Biotechnology Private small molecule ACI 91 for the treatment of Alzheimer's disease in Switzerland. The compound, developed using the company's Morphomer™ technology platform, has the 7 potential to prevent or slow down Alzheimer's disease by a dual mechanism of neuroprotection and plaque reduction correlated with an inhibition of beta-secretase, an amyloid precursor protein secretase [CONT.] AC Immune Owner Switzerland Biotechnology Private Affitope AD02 AFFiRiS GmbH and GlaxoSmithKline Biologicals AD 02 Amyloid beta-protein inhibitors Alzheimer's disease Phase II SC Austria, Croatia, Czech Republic, France, Germany, Slovakia AFFiRiS Originator Austria Biotechnology Private are developing affitope AD 02, a subunit vaccine targeting amyloid-beta (Abeta) protein, for the treatment of Alzheimer's disease (AD). The 8 antigenic component of the vaccine uses the N- terminal end of Abeta and was developed using AD 2 Immunostimulants AFFiRiS Owner Austria Biotechnology Private AFFiRiS' affitope technology platform AD02 GlaxoSmithKline Biologicals Licensee World Biotechnology Public (Affitome®). [CONT.] Alzheimer AD02 AVN 101 Avineuro Pharmaceuticals is developing AVN 101, AVN-101 Serotonin 6 receptor antagonists Alzheimer's disease Phase II Unknown route USA Avineuro Pharmaceuticals Licensee World Pharmaceutical Private a small-molecule, serotonin 5-HT6 receptor antagonist, for use as a cognitive enhancer in patients with Alzheimer's disease (AD) and in the treatment of anxiety. The compound was 9 originally discovered by the contract research organisation, ChemDiv, and was subsequently licensed to Avineuro. Phase II development of AVN 101 is underway in the US. Anxiety disorders Phase II Unknown route USA ChemDiv Originator USA CRO Private ChemDiv Owner USA CRO Private AVN 397 Avineuro Pharmaceuticals (US) is developing AVN AVN-397 Undefined mechanism Alzheimer's disease Phase II Unknown route USA Avineuro Pharmaceuticals Originator USA Pharmaceutical Private 397, a small molecule, for the treatment of 10 anxiety and Alzheimer's disease. This agent entered phase II development in June 2009. Anxiety disorders Phase II Unknown route USA Avineuro Pharmaceuticals Owner USA Pharmaceutical Private AZD 1446 AZD 1446 is a small molecule, alpha4beta2 AZD1446 Alpha4 beta2 nicotinic receptor agonists Alzheimer's disease Phase II PO Czech Republic, Hungary, Russia, Slovakia, Ukraine AstraZeneca Licensee World Large Pharma, Pharmaceutical Public nicotinic receptor agonist being developed by AstraZeneca for the treatment of Alzheimer's 11 disease. Phase II development is underway in this indication. Phase II development of AZD TC 6683 Alzheimer's disease (In volunteers) Phase I PO Japan Targacept Originator USA Biopharmaceutical Public 1446 for the treatment of attention-deficit TC-6683 Alzheimer's disease (In volunteers:Trials completed) Phase I PO Sweden Targacept Owner USA Biopharmaceutical Public hyperactivity disorder (ADHD) was discontinued. Attention-deficit hyperactivity disorder Discontinued(II) PO USA [CONT.] AZD 5213 AstraZeneca is developing the small molecule AZD5213 Histamine H3 receptor antagonists Alzheimer's disease Phase II PO USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public compound AZD 5213, a histamine H3 receptor antagonist, for the treatment of Alzheimer's disease and Gilles de la Tourette's syndrome. 12 Histamine H3 receptors control histamine synthesis and release in the central nervous Mild cognitive impairment Phase II PO USA AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public system, while inhibiting the release of other Alzheimer's disease (In volunteers) Phase I PO Japan, Sweden, USA neurotransmitters including dopamine, serotonin Attention-deficit hyperactivity disorder (In volunteers) No development reported(I) PO Japan, Sweden, USA and norepinephrine. [CONT.] BAN 2401 BioArctic Neuroscience and Eisai are jointly BAN-2401 Amyloid beta-protein inhibitors Alzheimer's disease (Early-stage disease) Phase II Parenteral United Kingdom, USA BioArctic Neuroscience Originator Sweden Biotechnology Private developing BAN 2401, a humanised monoclonal antibody originated by BioArctic, for the treatment of Alzheimer's disease. BAN 2401 13 selectively binds to and eliminates amyloid beta- peptide protofibrils, a soluble aggregate of amyloid beta-peptide thought to play a role in BAN2401 BioArctic Neuroscience Owner Sweden Biotechnology Private the development of Alzheimer's disease. [CONT.] Eisai Co Ltd Licensee World Large Pharma, Pharmaceutical Public Bapineuzumab Bapineuzumab is a humanised monoclonal AAB-001 Amyloid beta-protein inhibitors Alzheimer's disease Phase II SC USA Elan Corporation Originator Ireland Large Pharma, Biotechnology Public antibody that is designed to specifically target amyloid-beta (Abeta) in the brain. Pfizer and JANSSEN Alzheimer Immunotherapy are co- developing this product for the treatment of 14 Alzheimer's disease (AD). The product was AAB-001 SubQ Immunosuppressants Alzheimer's disease Discontinued(III) IV Australia, Canada, Europe, Japan, Mexico, South Africa, JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical undergoing phase III development for AD South America, USA (Fast Track) worldwide as an intravenous (IV) formulation. MedImmune Technology Provider USA Biotechnology Public However, development of the IV formulation was Pfizer Owner USA Large Pharma, Pharmaceutical Public discontinued [CONT.] Wyeth Originator USA Large Pharma, Pharmaceutical Public CAD 106 Cytos Biotechnology and Novartis in Switzerland Alzheimer's disease vaccine (CAD106) - Amyloid beta-protein inhibitors Alzheimer's disease Phase II IM Canada, European Union, Norway, Switzerland, USA Cytos Biotechnology Originator Switzerland Biotechnology Public are collaborating in the development of CAD 106 Cytos/Novartis for the potential treatment of Alzheimer's disease. CAD 106 treatment aims to generate antibodies against the beta-amyloid protein and 15 inhibit beta-amyloid plaque formation. CAD 106 consists of two components, the Immunodrug™ CAD106 Immunomodulators Alzheimer's disease Phase II SC European Union, Switzerland, USA Cytos Biotechnology Owner Switzerland Biotechnology Public carrier Qb coupled with a fragment of the beta- Immunodrug™ for Alzheimer's disease - Immunostimulants Hypersensitivity Discontinued(Preclinical) Unknown route Switzerland Novartis Licensee World Large Pharma, Pharmaceutical Public amyloid-protein. [CONT.] Cytos/Novartis Rheumatoid arthritis Discontinued(Preclinical) Unknown route Switzerland CERE 110 Ceregene is developing CERE 110, a gene AAV-NGF Gene expression stimulants Alzheimer's disease Phase II Intracranial USA Ceregene Licensee World Biotechnology Private therapy for the treatment of Alzheimer's disease (AD). The therapy employs the company's proprietary adeno-associated viral (AAV) vector system to deliver a gene for a neurotrophic factor, nerve growth factor (NGF), in an attempt 16 to prevent cell death and reverse cell atrophy. The therapy is surgically injected into the Nucleus Basalis of Meynert, a region of the brain in which Alzheimer's disease gene therapy - Ceregene Nerve growth factor stimulants University of California, San Diego Originator USA University N/A cholinergic neurons commonly degenerate in patients with AD. CERE 110 is in clinical CERE-110 University of California, San Diego Owner USA University N/A development for AD in the US. [CONT.] NGF gene therapy Crenezumab Crenezumab is an anti-amyloid-beta (Abeta) Anti-Abeta mAb Amyloid beta-protein inhibitors Alzheimer's disease Phase II IV Canada, France, Germany, Spain, United Kingdom, USA AC Immune Originator Switzerland Biotechnology Private monoclonal antibody that was identified from a collaboration between AC Immune Ltd. and Anti-Abeta mAb Alzheimer's disease Phase II SC Canada, France, Germany, Spain, United Kingdom, USA Banner Alzheimers Institute Funder USA Institution N/A Genentech (Roche) for Alzheimer's disease (AD). 17 Intravenous and subcutaneous formulations are Anti-amyloid-beta monoclonal antibody Alzheimer's disease Preclinical IV Switzerland Genentech Licensee World Large Pharma, Biotechnology Public in phase II trials with Genentech in the US for the MABT5102A National Institutes of Health (USA) Funder USA Institution N/A treatment of AD. [CONT.] RG 7412 Universidad de Antioquia Originator Colombia University N/A RG7412 Dronabinol - Echo Echo Pharmaceuticals B.V. is developing a Delta(9)-tetrahydrocannabinol - Echo Cannabinoid receptor agonists Alzheimer's disease Phase II PO Netherlands Echo Pharmaceuticals Originator Netherlands Pharmaceutical Pharmaceuticals proprietary tablet formulation of dronabinol for Pharmaceutical the treatment of spasticity and pain in patients with multiple sclerosis (MS), neuropsychiatric 18 symptoms in Alzheimer's disease (AD) and pain associated with chronic pancreatitis or post- surgical abdominal pain. The product is in phase Delta(9)-THC - Echo Pharmaceutical Multiple sclerosis Phase II PO Netherlands Echo Pharmaceuticals Owner Netherlands Pharmaceutical II clinical development in the Netherlands. ECP022A (delta9-THC) Pain Phase II PO Netherlands University Medical Centre of Nijmegen Collaborator Netherlands University N/A [CONT.] Namisol® VU University Medical Center Collaborator Netherlands University N/A ELND 005 ELND 005 is a small molecule compound that is AZD 103 Amyloid beta-protein inhibitors Alzheimer's disease Phase II PO Canada, Spain, USA (Fast Track) Elan Corporation Licensee World Large Pharma, Biotechnology Public being developed by Speranza Therapeutics for the treatment of Alzheimer's disease (AD), and AZD-103 Bipolar disorders (Adjunctive treatment) Phase II PO Bulgaria, Canada, Czech Republic, Lithuania, Romania, PPD Collaborator World CRO Public bipolar disorder. Transition Therapeutics Spain, USA originated ELND 005 and has licensed it to 19 AZD103 Speranza Therapeutics Sub-licensee World Pharmaceutical Speranza worldwide. The orally administered ELND005 Transition Therapeutics Originator Canada Biopharmaceutical Public agent appears to prevent and reverse the Quercinitol Transition Therapeutics Owner Canada Biopharmaceutical Public fibrilisation (aggregation into insoluble plaques) of Scyllitol amyloid-beta (Abeta) peptides in the brain Scyllo-cyclohexanehexol [CONT.] Scyllo-inositol Etazolate Etazolate is a small molecule, oral compound EHT 0202 Amyloid precursor protein secretase inhibitors Alzheimer's disease (Adjunctive treatment) Phase II PO France Diaxonhit Owner France Pharmaceutical belonging to a family of pyrazolopyridines, in EHT 202 GABA A receptor modulators Parkinson's disease Discontinued(I) PO France ExonHit Therapeutics Originator France Technology provider Public 20 clinical development with Diaxonhit (formerly ExonHit Therapeutics) in France for the EHT-0202 Type 4 cyclic nucleotide phosphodiesterase Retinal disorders Discontinued(I) PO France treatment of neurodegenerative disorders, inhibitors including Alzheimer's disease (AD). [CONT.] EHT0202 Vascular dementia Discontinued(Preclinical) PO France EVP 0962 EnVivo Pharmaceuticals is developing EVP 0962, EVP 0015962 Amyloid precursor protein secretase modulators Alzheimer's disease Phase II PO USA EnVivo Pharmaceuticals Originator USA Biopharmaceutical Private an orally available, small molecule, selective gamma secretase (gamma-secretase) modulator 21 for the treatment of Alzheimer's disease (AD). EVP 0962 is brain-permeable and has disease- modifying potential. Phase II clinical development EVP-0015962 EnVivo Pharmaceuticals Owner USA Biopharmaceutical Private is underway in the US. [CONT.] EVP-0962 GM 6 Genervon is developing a first-in-class peptide GM6 1 Phosphatidylinositol 3 kinase modulators Amyotrophic lateral sclerosis Phase II IV USA (Fast Track) Genervon Biopharmaceuticals Originator USA Biopharmaceutical Private therapeutic, GM 6, for the treatment of neurological disorders. Genervon discovered motoneuronotrophic factor (MNTF) that highly expressed during week nine of embryonic GM602 Apoptosis inhibitors Parkinson's disease Phase II IV USA Genervon Biopharmaceuticals Owner USA Biopharmaceutical Private development, and is a master regulator of the 22 GM603 Bcl-X protein inhibitors Stroke Phase II IV USA embryonic nervous system. This discovery led to GM604 Free radical inhibitors Alzheimer's disease (In volunteers) Phase I IV USA the development of GM 6; GM 6 is a six amino GM605 Insulin receptor modulators Multiple sclerosis (In volunteers) Phase I IV USA acid analogue of one of the active sites of human GM606 Nervous system modulators Spinal cord injuries (In volunteers) Phase I IV USA MNTF and one of nine from a patented family of GM607 Neurogenesis modulators Musculoskeletal disorders Preclinical IV USA human master regulators of the nervous system GM608 Proto oncogene protein c akt modulators Huntington's disease Research IV USA [CONT.] GM609 GSK 239512 GlaxoSmithKline (GSK) is developing GSK 239512 Alzheimer's disease Phase II PO Chile, European Union, Russia, South Korea GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public 239512, an orally active histamine H3 receptor antagonist, for the treatment of cognition 23 disorders. Phase II trials for the treatment of Alzheimer's disease and schizophrenia have been GSK239512 Multiple sclerosis Phase II PO Bulgaria, Germany, Spain, Sweden, United Kingdom GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public conducted; phase II development in multiple Schizophrenia Phase II PO USA sclerosis has been initiated in several European Alzheimer's disease Phase I PO Australia countries. GSK 933776A GSK 933776A is an anti-beta amyloid monoclonal 933776 Amyloid beta-protein inhibitors Dry age-related macular degeneration Phase II IV USA GlaxoSmithKline Originator United Kingdom Large Pharma, Pharmaceutical Public antibody being developed by GlaxoSmithKline for intravenous administration in the treatment of Alzheimer's disease and dry age-related macular 24 degeneration (geographic atrophy secondary to Alzheimer's disease vaccine - GlaxoSmithKline Alzheimer's disease Phase I IV Australia, Germany, Norway, Sweden GlaxoSmithKline Owner United Kingdom Large Pharma, Pharmaceutical Public age-related macular degeneration). GSK 933776A is in phase I development for the GSK 933776 treatment of AD in Europe and Australia. [CONT.] GSK-933776 GSK933776A HF 0220 Newron Pharmaceuticals (previously Hunter- 7beta-hydroxy-epiandrosterone Antioxidants Alzheimer's disease Phase II PO India, Sweden, United Kingdom Hunter-Fleming Originator United Kingdom Biopharmaceutical Private Fleming) is developing HF 0220, an orally administered 7-hydroxyderivative of epiandrosterone (7beta-OH-EPIA) with anti- glucocorticoid and neuroprotective effects, for 25 the treatment of neurodegenerative disorders and inflammatory diseases. The company has carried out phase II trials of HF 0220 for the 7beta-OH-EPIA Glucocorticoid receptor antagonists Rheumatoid arthritis Phase I PO United Kingdom Newron Pharmaceuticals Owner Italy Biopharmaceutical Public treatment of Alzheimer's disease (AD) and a HF0220 Inflammatory bowel diseases Discontinued(Preclinical) PO United Kingdom phase I study in rheumatoid arthritis (RA). Psoriasis Discontinued(Preclinical) PO United Kingdom [CONT.] Ispronicline Ispronicline is a CNS-selective, nicotinic receptor AZD 3480 Alpha4 beta2 nicotinic receptor agonists Alzheimer's disease Phase II PO Czech Republic, Romania, Slovakia, Ukraine, USA R. J. Reynolds Tobacco Company Originator USA Company partial agonist that is being developed by Targacept (formerly a subsidiary of R.J. Reynolds Tobacco Company) for the treatment of AZD-3480 Attention-deficit hyperactivity disorder Discontinued(II) PO USA Targacept Originator USA Biopharmaceutical Public Alzheimer's disease (AD). This orally active, small 26 AZD3480 Cognition disorders Discontinued(II) PO Canada, USA molecule is selective for the alpha4beta2- RJR 1734 Cognition disorders (In volunteers) Discontinued(I) PO Japan containing nicotinic receptor subtypes in the RJR-1734 brain, which have been associated with nicotinic TC 01734 cholinergic modulation of learning and memory TC 1734 processes [CONT.] TC-1734 Ladostigil Ladostigil is a cholinesterase and brain-selective Ladostigil hemitartrate Cholinesterase inhibitors Alzheimer's disease Phase II PO Austria, Croatia, Germany, Serbia, Spain Avraham Pharmaceuticals Licensee Israel Pharmaceutical Private monoamine oxidase (MAO) inhibitor that is being developed by Avraham Pharmaceuticals as an oral treatment for Alzheimer's disease and mild 27 cognitive impairment. The agent is designed to TV 3326 Monoamine oxidase inhibitors Mild cognitive impairment Phase II PO Austria, Germany, Israel Hebrew University of Jerusalem Originator Israel University N/A provide a combination of the improved cognitive TV-3326 Hebrew University of Jerusalem Owner Israel University N/A function exhibited by inhibitors of cholinesterase TV3326 Rappaport Institute Collaborator Israel Institution N/A (i.e. [CONT.] Yissum Research Development Company Technology Transfer Israel Technology Transfer Private Lu AE 58054 Lu AE 58054 is an orally active, serotonin 6 (5- LU AE58054 Serotonin 6 receptor antagonists Alzheimer's disease (Adjunctive treatment) Phase II PO Australia, Canada, Czech Republic, Germany, Italy, Poland, Asterand plc Technology Provider USA Pharmaceutical Public HT6) receptor antagonist, which is being Spain developed by Lundbeck for the treatment of LUAE 58054 Cognition disorders (Adjunctive treatment:Cognitive Phase II PO Belgium, France, Hong Kong, Italy, Poland, Taiwan, Eli Lilly Originator USA Large Pharma, Pharmaceutical Public cognitive impairment associated with impairment associated with schizophrenia (CIAS)) Thailand 28 schizophrenia (CIAS) and for Alzheimer's disease. SGS 518 Cognition disorders Phase II PO USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public The serotonin 6 receptor is primarily found in SGS-518 Lundbeck A/S Licensee World Large Pharma, Pharmaceutical Public areas of the brain involved in cognition. [CONT.] SGS518 Otsuka Pharmaceutical Sub-licensee Asia, Canada, Europe, Japan, USA Pharmaceutical Private

Methanesulfonyl fluoride SeneXta Therapeutics is developing SNX-001 Acetylcholinesterase inhibitors Alzheimer's disease Phase II PO Mexico SeneXta Therapeutics Licensee World Biopharmaceutical methanesulfonyl fluoride, SNX 001, as a novel, long-acting, oral inhibitor of acetylcholinesterase (AChE) for the treatment of Alzheimer's disease and post stroke cognitive impairment. 29 Methanesulfonyl fluoride was originally developed by the University of Texas at El Paso. Initial exploratory non-GLP (Good Laboratory Practice) trials (phase I and II) in the Alzheimer's disease indication were completed in Mexico [CONT.] SNX001 Alzheimer's disease Phase I PO Germany The University of Texas at El Paso Originator USA Cognition disorders Preclinical PO USA The University of Texas at El Paso Owner USA MSDC 0160 Metabolic Solutions Development Company is Mitoglitazone™ Mitochondrial protein stimulants Alzheimer's disease Phase II PO USA Metabolic Solutions Development Company Originator USA Pharmaceutical Private developing MSDC 0160 (Mitoglitazone™), a once daily, oral peroxisome proliferator-activated receptor gamma (PPARgamma)-sparing insulin sensitiser, for the treatment of type 2 diabetes 30 mellitus, Alzheimer's disease and polycystic kidney disease. MSDC 0160 is undergoing phase II development for type 2 diabetes mellitus and MSDC-0160 MTOR protein inhibitors Type 2 diabetes mellitus Phase II PO USA Metabolic Solutions Development Company Owner USA Pharmaceutical Private Alzheimer's disease in the US [CONT.] Polycystic kidney disease Preclinical PO USA PKD Foundation Collaborator USA Institution N/A University of Illinois at Chicago Collaborator USA University N/A NIC 515 Humanetics Corporation and Mount Sinai School NIC5 15 Amyloid precursor protein secretase inhibitors Alzheimer's disease Phase II PO USA Humanetics Corporation Licensee USA Pharmaceutical Private of Medicine are developing NIC 515 as an oral agent for the treatment of Alzheimer's disease (AD). NIC 515, a small naturally occurring molecule, is a potent insulin sensitiser. The 31 compound also prevents certain peptides from aggregating to form beta amyloid plaques associated with Alzheimer's disease and improves cognitive function in mice with AD type neuropathology and memory impairment [CONT.] NIC5-15 Mount Sinai School of Medicine Originator USA University N/A Mount Sinai School of Medicine Owner USA University N/A ORM 12741 Orion Pharma is developing an oral alpha2c ORM-12741 Alpha 2c adrenergic receptor antagonists Alzheimer's disease Phase II PO Finland, Spain Orion Originator Finland Pharmaceutical Public adrenergic receptor antagonist, ORM 12741, for the treatment of Alzheimer's disease. A phase II trial in this indication has been completed in 32 Finland and Spain. Phase II trial development in the treatment of Raynaud's disease was discontinued. ORM 12741 was also in phase II Raynaud's disease Discontinued(II) PO United Kingdom Orion Owner Finland Pharmaceutical Public development for the treatment of schizophrenia. Schizophrenia No development reported(II) PO Europe [CONT.] PBT 2 PBT 2 is a second-generation, small molecule, PBT-2 Chelating agents Alzheimer's disease (Early-stage disease) Phase II PO Australia, Sweden Prana Biotechnology Originator Australia Biotechnology Public metal protein-attenuating compound (MPAC) that is in clinical development with Prana Biotechnology for the treatment of Alzheimer's 33 disease (AD) and Huntington's disease (HD). It is an 8-hydroxyquinoline derivative that targets the PBT2 Huntington's disease (Early-stage disease, Mid-stage Phase II PO Australia, USA Prana Biotechnology Owner Australia Biotechnology Public interaction between metals and beta-amyloid disease) (Abeta) in the synapse. [CONT.] Huntington's disease (In volunteers) Phase I PO Netherlands PF 5212377 Pfizer is developing PF 5212377, a small PF-05212377 Serotonin 6 receptor antagonists Alzheimer's disease (Adjunctive treatment) Phase II PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public molecule, serotonin 6 receptor (5-HT6) antagonist for the treatment of Alzheimer's disease. Serotonin 6 receptor antagonists may 34 improve deficits in learning and memory by increasing levels of the neurotransmitters acetylcholine and glutamate. PF 5212377 was PF-5212377 Alzheimer's disease (In volunteers) Phase I PO France Wyeth Originator USA Large Pharma, Pharmaceutical Public originally developed by Wyeth as WYE 103760, SAM-760 also referred to as SAM 760. [CONT.] WYE-103760 PM 012 The South Korean-based company PuriMED is PM012 tablet - PuriMED Alzheimer's disease Phase II PO South Korea PuriMED Originator South Korea Biotechnology Private developing a herbal-based medicine called PM 012, which is intended for the prevention of dementia, specifically that related to Alzheimer's disease. While the specific components of PM 012 35 are unknown, the company has indicated that this herbal medicine has the potential to increase the learning ability in young people and prevented forgetfulness in elderly subjects [CONT.] PuriMED Owner South Korea Biotechnology Private R-phenserine QR Pharma, under a licence from Raptor (+)-(3aR)-phenserine Acetylcholinesterase inhibitors Alzheimer's disease Phase II PO USA Cenomed BioSciences Licensee World Biopharmaceutical Private Pharmaceutical Corp. (formerly TorreyPines Therapeutics), is developing R-phenserine, the R- enantiomer (positive isomer) of phenserine, for the treatment of Alzheimer's disease (AD) and 36 Parkinson's disease (PD). The compound has also (+)-phenserine Alpha-synuclein inhibitors Mild cognitive impairment Phase II PO USA Massachusetts General Hospital Collaborator USA Hospital N/A been licensed to Cenomed BioSciences, who will Posiphen® Amyloid beta-protein precursor inhibitors Parkinson's disease Phase II PO USA National Institute on Aging Originator USA Institution N/A develop it for the treatment of poisoning Tau protein inhibitors Poisoning Preclinical PO USA National Institutes of Health (USA) Originator USA Institution N/A following exposure to organophosphorous nerve QR Pharma Licensee World Biotechnology agents [CONT.] Raptor Pharmaceutical Corp Originator USA Pharmaceutical Public RG 1577 Roche is developing RG 1577 (also known as EVT EVT-302 Monoamine oxidase B inhibitors Alzheimer's disease (Adjunctive treatment, Combination Phase II PO Australia, Canada, Czech Republic, France, Germany, Italy, Evotec AG Licensee World Pharmaceutical Public 302), a selective and reversible monoamine therapy) Poland, South Korea, Spain, Sweden, USA oxidase B (MAO-B) inhibitor, for the treatment of Alzheimer's disease. Preclinical studies of RG 37 EVT302 Alzheimer's disease Phase I PO Japan Roche Originator Switzerland Large Pharma, Pharmaceutical Public 1577 showed a superior safety profile to that of RG-1577 Alzheimer's disease (In volunteers) Phase I PO Netherlands Roche Owner Switzerland Large Pharma, Pharmaceutical Public already marketed MAO-B inhibitors, and RG1577 Smoking withdrawal Discontinued(II) PO Germany Roche Sub-licensee World Large Pharma, Pharmaceutical Public improved tolerability compared with current RO-4602522 Smoking withdrawal Discontinued(I) PO Finland, United Kingdom treatments for nicotine dependence. [CONT.] RO4602522 Rilapladib Rilapladib, an oral inhibitor of lipoprotein- 659032 1-alkyl-2-acetylglycerophosphocholine esterase Alzheimer's disease Phase II PO Bulgaria, Germany, Italy, Norway, Spain, Sweden GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public associated phospholipase A2 (Lp-PLA2), was inhibitors discovered as part of a collaboration between GlaxoSmithKline (GSK) and Human Genome Sciences (now a GSK subsidiary). Phase I 38 development appears to have been completed and the compound has moved into phase II studies in patients with atherosclerosis in the USA. Phase II clinical development is also underway for Alzheimer's disease. [CONT.] Rilapladib Rilapladib, an oral inhibitor of lipoprotein- 1-alkyl-2-acetylglycerophosphocholine esterase associated phospholipase A2 (Lp-PLA2), was inhibitors discovered as part of a collaboration between GlaxoSmithKline (GSK) and Human Genome Sciences (now a GSK subsidiary). Phase I 38 development appears to have been completed and the compound has moved into phase II GSK 659032 Atherosclerosis Phase II PO USA Human Genome Sciences Originator USA Biopharmaceutical Public studies in patients with atherosclerosis in the GSK659032 USA. Phase II clinical development is also SB 659032 underway for Alzheimer's disease. [CONT.] SB-659032 RVX 208 Resverlogix is developing RVX 208, an orally RVX 000222 Apolipoprotein A I stimulants Acute coronary syndromes Phase II PO Argentina, Brazil, European Union, Russia, USA Cedars-Sinai Health System Collaborator USA Institution N/A available, small-molecule, bromodomain and extraterminal domain (BET) protein inhibitor, which increases apolipoprotein AI (ApoA-I) and HDL-cholesterol levels. The first-in-class 39 compound was developed using Resverlogix's NexVas™ technology, and is designed to treat RVX-000222 Bromodomain and extraterminal domain protein Atherosclerosis Phase II PO Argentina, Brazil, European Union, Russia, USA Resverlogix Corporation Originator Canada Biotechnology Public cardiovascular disorders, including inhibitors atherosclerosis, cerebrovascular disease and RVX-208 Low HDL cholesterol Phase II PO South Africa Resverlogix Corporation Owner Canada Biotechnology Public hypertension, and Alzheimer's disease (AD) RVX000222 Prediabetic-state Phase II PO Australia [CONT.] RVX208 Alzheimer's disease Phase I PO USA S 38093 S 38093 is a histamine H3 receptor antagonist S38093 Histamine H3 receptor antagonists Alzheimer's disease Phase II PO United Kingdom Servier Originator France Pharmaceutical Private that is being developed by Servier for the treatment of Alzheimer's disease. Phase II 40 development of the agent is ongoing in the UK, and is expected to soon be initiated in a number of other countries throughout the EU and Servier Owner France Pharmaceutical Private globally. SAR 110894 Sanofi (formerly sanofi-aventis) is developing SAR110894 Histamine H3 receptor antagonists Alzheimer's disease Phase II PO Australia, Canada, France, Germany, Italy, Poland, Portugal, Sanofi Owner France Large Pharma, Pharmaceutical Public SAR 110894, a histamine H3 receptor antagonist, Spain, USA for the treatment of Alzheimer's disease. The H3 receptor is a G-protein coupled receptor that is predominantly expressed in the central nervous system. These autoreceptors negatively regulate 41 the release of neurotransmitters including dopamine, norepinephrine, acetylcholine and histamine and are believed to play a role in the regulation of feeding, cognition, arousal, pain and endocrine systems [CONT.] SAR110894D sanofi-aventis Originator France Large Pharma, Pharmaceutical Public Sarsasapogenin Phytopharm is developing sarsasapogenin, an Cogane™ Brain derived neurotrophic factor agonists Alzheimer's disease Phase II PO United Kingdom Phytopharm Originator England Pharmaceutical Public orally active, small molecule, non-peptide, nerve growth factor stimulant, for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease 42 (PD) and amyotrophic lateral sclerosis (ALS). Additional potential indications include glaucoma, vascular dementia, mild cognitive impairment, PYM-50028 Glial cell line-derived neurotrophic factor agonists Parkinson's disease (Early-stage disease) Phase II PO Canada, Czech Republic, France, Germany, Hungary, Phytopharm Owner England Pharmaceutical Public diabetic neuropathy and neuropsychiatric Poland, Romania, Serbia, United Kingdom, USA disorders, such as schizophrenia, depression, PYM50028 Neuron stimulants Amyotrophic lateral sclerosis Preclinical PO United Kingdom anxiety and epilepsy [CONT.] Glaucoma Preclinical PO United Kingdom SB 742457 SB 742457 is an oral serotonin (5-HT)6 receptor 742457 Serotonin 6 receptor antagonists Alzheimer's disease (Combination therapy:Add-on to Phase II PO Argentina, Australia, Canada, Chile, European Union, USA GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public antagonist in phase II development with donepezil) GlaxoSmithKline (GSK) for the treatment of 43 GSK 742457 Alzheimer's disease Phase II PO Chile, Croatia, European Union, Mexico, New Zealand, GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public Alzheimer's disease. SB 742457 undergone trials Russia, South Africa, South Korea as a monotherapy, and as an add-on treatment SB-742457 Alzheimer's disease (In volunteers) Phase I PO USA to donepezil. Sodium oligomannurarate Shanghai Green Valley Pharmaceutical is Sodium oligo-mannurarate Undefined mechanism Alzheimer's disease Phase II PO China Shanghai Green Valley Pharmaceutical Originator China Manufacturer developing sodium oligomannurarate for the treatment of Alzheimer's disease. A phase II 44 clinical trial is assessing the efficacy and tolerability of sodium oligomannurarate capsules in approximately 252 subjects with mild to moderate Alzheimer's disease from China Shanghai Green Valley Pharmaceutical Owner China Manufacturer (NCT01453569). Sodium phenylbutyrate - Digna Digna Biotech is developing the small-molecule 4-PBA Histone deacetylase inhibitors Alzheimer's disease Phase II Unknown route Europe Digna Biotech Originator Spain Biotechnology Private Biotech compound sodium phenylbutyrate (4-PBA) as a therapy for Alzheimer's disease in clinical trials in Europe. The University of Navarra in Pamplona, 45 Spain, is also involved in the development of this agent. Digna Biotech is a spin-off company of the Centre for Applied Medical Research of the University of Navarra. [CONT.] University of Navarra Originator Spain University N/A Sodium selenate - Velacor Velacor Therapeutics is developing sodium VEL 015 Protein phosphatase 2A stimulants Alzheimer's disease (Early-stage disease) Phase II PO Australia Velacor Therapeutics Originator Australia Pharmaceutical Therapeutics selenate, as an oral capsule, for the treatment of Alzheimer's disease. The compound acts to restore the activity of protein phosphatase 2a 46 (PP2A), which is responsible for cleaving phosphatase from tau. Tau stablises the microtubule transport system in neurons and hyperphosphorylation of tau causes tau tangles VEL-015 Velacor Therapeutics Owner Australia Pharmaceutical seen in Alzheimer's disease. [CONT.] VEL015 ST 101 Sonexa Pharmaceuticals, under an exclusive ST101 Acetylcholine stimulants Alzheimer's disease Phase II PO Canada, USA Sonexa Therapeutics Licensee USA Biopharmaceutical Private license from Zenyaku Kogyo in Japan, is developing an orally active, first-in-class, small- molecule compound ST 101, an azaindolizinone derivative, for the treatment of Alzheimer's 47 disease (AD) and essential tremor. ST 101 has been demonstrated to stimulate acetylcholine release in the hippocampus and cerebral coretex, ZSET 1446 Essential tremor Phase II PO USA Zenyaku Kogyo Originator Japan Pharmaceutical Private and has also reduced cognitive impairment in ZSET-1446 Zenyaku Kogyo Owner Japan Pharmaceutical Private animal models [CONT.] ZSET1446 T 817MA T 817MA is an orally available, benzothiophenyl T-817MA Amyloid beta-protein inhibitors Alzheimer's disease Phase II PO USA Toyama Chemical Originator Japan Pharmaceutical Public derivative with neuroprotective activity that is being developed by Toyama Chemical for the treatment of Alzheimer's disease (AD). This neurotrophic agent prevents amyloid-beta 48 (Abeta)-induced neurodegeneration and promotes neurite outgrowth. Preclinical studies suggest T 817MA may improve cognition by reducing oxidative stress. [CONT.] T817MA Alzheimer's disease Phase I PO Japan Toyama Chemical Owner Japan Pharmaceutical Public TC 5619 Targacept is developing TC 5619, an orally TC-0569 Alpha7 nicotinic acetylcholine receptor agonists Cognition disorders (Adjunctive treatment:In patients with Phase II PO Eastern Europe, USA Targacept Originator USA Biopharmaceutical Public administered small molecule that is highly schizophrenia) selective for the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR). The alpha7 nAChR is 49 associated with sensory gating and cognition, and TC-5619 Cognition disorders (Adjunctive treatment:In patients with Phase II PO India Targacept Owner USA Biopharmaceutical Public compounds that modulate this target could play a schizoprenia) role in the protection of neuronal cells from TC-5619-238 Alzheimer's disease Phase I PO USA deterioration and death. [CONT.] TC5619 Attention-deficit hyperactivity disorder Discontinued(II) PO USA TTP 488 TTP 488 is an orally administered, small molecule PF 04494700 Advanced glycosylation end-product receptor Alzheimer's disease Phase II PO USA (Fast Track) TransTech Pharma Originator USA Pharmaceutical Private drug candidate that is being developed by antagonists TransTech Pharma for the treatment of Alzheimer's disease. TTP 488 is an antagonist of the receptor for advanced glycation end (RAGE) 50 products, and appears to inhibit amyloid fibrillogenesis. The compound was undergoing joint research by TransTech Pharma and Pfizer PF-04494700 Amyloid inhibitors Diabetic nephropathies Discontinued(II) PO Canada TransTech Pharma Owner USA Pharmaceutical Private up until the latter ceased its activities for this PF-4494700 compound [CONT.] TTP488 Vanutide cridificar Pfizer and JANSSEN Alzheimer Immunotherapy Abeta immunotherapeutic conjugate Immunostimulants Alzheimer's disease Phase II IM France, Germany, Japan, Spain, USA Agenus Technology Provider USA Biotechnology Public are co-developing vanutide cridificar, an AAC 001 Boston Biomedical Research Institute Technology Provider USA Institution N/A immunoconjugate vaccine based around amyloid- AAC-001 Elan Corporation Originator Ireland Large Pharma, Biotechnology Public beta (Abeta) peptide, for the treatment of AAC001 JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical Alzheimer's disease (AD). The vaccine, which is ACC 001 Pfizer Owner USA Large Pharma, Pharmaceutical Public administered as an intramuscular injection, is ACC-001 Wyeth Originator USA Large Pharma, Pharmaceutical Public 51 generated through the conjugation of small N- ACC001 terminal peptide fragments of Abeta to a non- toxic diphtheria mutant carrier protein, CRM197 [CONT.] Vanutide cridificar Pfizer and JANSSEN Alzheimer Immunotherapy Immunostimulants are co-developing vanutide cridificar, an immunoconjugate vaccine based around amyloid- beta (Abeta) peptide, for the treatment of Alzheimer's disease (AD). The vaccine, which is administered as an intramuscular injection, is 51 generated through the conjugation of small N- terminal peptide fragments of Abeta to a non- Active beta-amyloid immunotherapeutic toxic diphtheria mutant carrier protein, CRM197 conjugate [CONT.] CRM 197 CRM197 Peptide-CRM Conjugate PF-05236806 PF-5236806 Velusetrag Velusetrag is a selective serotonin-4 (5-HT4) TD 5108 Serotonin 4 receptor agonists Constipation Phase II PO USA Alfa Wassermann SpA Collaborator Italy Pharmaceutical Private receptor agonist that is being developed by Theravance as a once-daily oral prokinetic for the treatment of chronic constipation. Development is 52 also in progress for Alzheimer's disease. The drug was developed in collaboration with GlaxoSmithKline, through the application of multivalent drug design from the company's drug TD-5108 Gastroparesis Phase II PO USA Theravance Originator USA Biopharmaceutical Public discovery programme. [CONT.] TD5108 Alzheimer's disease Phase I PO USA Theravance Owner USA Biopharmaceutical Public VI 1121 VIVUS is developing VI 1121, a compound for the VI-1121 Undefined mechanism Alzheimer's disease (Adjunctive treatment) Phase II Unknown route USA VIVUS Originator USA Pharmaceutical Public treatment of Alzheimer's disease. The mechanism 53 of action and route of administration are undisclosed. The company is conducting a phase II clinical study in the US. VI1121 VIVUS Owner USA Pharmaceutical Public ACI 24 AC Immune is developing ACI 24 for the Immunostimulants Alzheimer's disease I/II Parenteral Scandinavia AC Immune Originator Switzerland Biotechnology Private treatment of Alzheimer's disease. The compound was developed using the company's antigen technology (SupraAntigen™) platform which induces changes in the conformation of misfolded 54 proteins, shifting the equilibrium in favour of benign forms. Incorrect processing of amyloid precursor protein (APP) generates the beta amyloid protein, the main component of the plaques found in the brains of Alzheimer's AC Immune Owner Switzerland Biotechnology Private patients [CONT.] Bayer HealthCare Pharmaceuticals Collaborator Germany Pharmaceutical Public Bryostatin 1 - Aphios Aphios is a biopharmaceutical company APH 0703 Protein kinase C stimulants Alzheimer's disease I/II IV Bahamas Aphios Corporation Originator USA Biopharmaceutical Private developing a natural therapeutic, called bryostatin 1, for certain cancers and CNS disorders. Bryostatin 1 is a protein kinase C APH-0703 Cognition disorders I/II IV Bahamas Aphios Corporation Owner USA Biopharmaceutical Private activator that has been isolated from sea moss 55 Bryosomes™ Alzheimer's disease Preclinical IV USA (Bugula neritina), which is found off the coast of Bryostatin 1-containing phospholipid nanosomes Alzheimer's disease Preclinical PO USA California, USA. Bryostatin 1 is an anticancer (Bryosomes™) - Aphios agent has entered more than 35 phase I and II Bryostatin-1 - Aphios Cognition disorders Preclinical IV USA clinical trials by the National Cancer Institute Nanoencapsulated APH 0703 Cognition disorders Preclinical PO USA (NCI) and others for melanomas, lymphomas and Oesophageal cancer (New delivery system) Preclinical Parenteral USA LY 2886721 Eliother Lilly cancers. is developing [CONT.] LY 2886721, an orally beta secretase inhibitor - Eli Lilly Alzheimer's disease I/II PO Italy, Japan, Netherlands, Spain, USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public available, small molecule inhibitor of the BACE1 protein, for the treatment of patients with Alzheimer's disease (AD). Cleavage of the 56 amyloid precursor protein by BACE1 is one of the necessary steps in the formation of amyloid beta, and so inhibition of the enzyme is expected to halt progression of the disease. [CONT.] LY2886721 Alzheimer's disease (In volunteers) Phase I PO USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public Nilvadipine - Archer Archer Pharmaceuticals is developing a ARC 029 Calcium channel antagonists Alzheimer's disease I/II Unknown route Europe Archer Pharmaceuticals Originator USA Pharmaceutical Private Pharmaceuticals proprietary formulation of nilvadipine for the treatment of Alzheimer's disease (AD). This drug may be the first member of a new class of drugs 57 known as soluble amyloid reducing/clearing agents (SARC). Nilvadipine, a calcium channel blocker, is widely used in the treatment of hypertension (since 1991) and studies suggest it has pro-cognitive functions. [CONT.] ARC029 Alzheimer's disease Phase I Unknown route USA Archer Pharmaceuticals Owner USA Pharmaceutical Private RPh 201 Regenera Pharma is developing RPh 201, a RPh201 Undefined mechanism Alzheimer's disease I/II SC Canada Regenera Pharma Originator Israel Pharmaceutical Private proprietary formulation of a well-defined and characterised botanical drug, for the treatment of neurodegenerative diseases, burns and chronic wounds. RPh 201 is being developed with the 58 company's novel, proprietary extraction and purification processes. RPh 201 has demonstrated unprecedented neuroregeneration Chronic wounds I/II Topical Israel Regenera Pharma Owner Israel Pharmaceutical Private in well-established animal models of stroke and Burns Preclinical Topical Israel dementia [CONT.] Neurodegenerative disorders Preclinical Parenteral Israel AAB 003 Wyeth (Pfizer) and JANSSEN Alzheimer AAB-003 Amyloid beta-protein inhibitors Alzheimer's disease Phase I IV South Korea, USA Elan Corporation Originator Ireland Large Pharma, Biotechnology Public Immunotherapy are collaborating on the development of AAB 003, an intravenously administered monoclonal antibody that targets and inhibits beta-amyloid (Abeta) peptide, for the treatment of Alzheimer's disease (AD). The 59 product is in phase I clinical development in the US and South Korea. The compound was initially being developed by AAB003 JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical Wyeth and Elan. [CONT.] PF-05236812 Pfizer Owner USA Large Pharma, Pharmaceutical Public Wyeth Originator USA Large Pharma, Pharmaceutical Public AAD 2004 AAD 2004 is a sulfasalazine-derived small AAD-2004 Amyloid beta-protein inhibitors Alzheimer's disease Phase I Unknown route European Union AmKor Pharma Collaborator USA Biotechnology Private molecule that is being developed by GNT Pharma in South Korea and its US subsidiary, AmKor Pharma for the treatment of Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic 60 lateral sclerosis (ALS). The drug provides neuroprotection via both antioxidative and anti- inflammatory effects, as well as the inhibition and AAD2004 Antioxidants Amyotrophic lateral sclerosis Phase I Unknown route European Union GNT Pharma Owner South Korea Pharmaceutical Public reduction of beta-amyloid (Abeta) peptide levels Dinoprostone antagonists Parkinson's disease Phase I Unknown route European Union Neurotech Pharmaceuticals Originator South Korea Pharmaceutical Public and Abeta plaque formation [CONT.] Free radical scavengers Toyota Tsusho Corporation Market Licensee Japan Company Public Prostaglandin synthase inhibitors AADvac 1 Axon Neuroscience is developing AADvac 1, a tau AADvac1 Immunostimulants Alzheimer's disease Phase I SC Austria Axon Neuroscience Originator Slovakia Biotechnology peptide-KLH conjugate active vaccine for the treatment of Alzheimer's disease. The vaccine targets misfolded tau protein, and is expected to 61 prevent cognitive decline through reducing neurofibrillary tangles, removing hyperphosphorylated tau protein and reducing the amount of oligomerised and insoluble Alzheimer's disease vaccine - Axon Neuroscience Tau protein modulators Axon Neuroscience Owner Slovakia Biotechnology pathological tau in the brain. [CONT.] ABP 102 Abiogen Pharma is developing ABP 102 in clinical ABP-102 Amyloid beta-protein inhibitors Alzheimer's disease Phase I Parenteral Europe Abiogen Pharma Originator Italy Pharmaceutical Private trials in Europe for the treatment of Alzheimer's disease (AD). ABP 102 is an abzyme; these comprise anti-beta-amyloid (Abeta) monoclonal 62 antibodies fused to a peptide hydrolase (protease). Such catalytic monoclonal antibodies are designed as carriers of proteins with protease activity for selective lysis of beta-amyloid 1-42 protein (Abeta1-42), a [CONT.] ABP102 Abiogen Pharma Owner Italy Pharmaceutical Private ABT 957 AbbVie is developing ABT 957, a calpain inhibitor ABT-957 Calpain inhibitors Alzheimer's disease Phase I Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public for potential use in the treatment of Alzheimer's disease (AD). The over activation of calpain, a calcium-dependent cysteine protease, is believed to play a role in the pathophysiology of several neurodegenerative disorders, including AD. In 63 particular, the etiological pathway points to the hyperphosphorylation of the microtubule- associated protein tau and the subsequent aggregation of tau filaments causing the formation of neurofibrillary tangles [CONT.] AbbVie Owner USA Biopharmaceutical Public Affitope AD03 AFFiRiS and GlaxoSmithKline are collaborating on AD 03 Amyloid beta-protein inhibitors Alzheimer's disease Phase I SC Austria AFFiRiS Originator Austria Biotechnology Private the development of affitope AD03, a vaccine candidate for the treatment of Alzheimer's disease. The vaccine has been customised using 64 AFFiRiS' Affitope platform technology (Affitom®) AD03 Immunostimulants AFFiRiS Owner Austria Biotechnology Private and is designed to induce cross-reactive Affitope-AD03 GlaxoSmithKline Licensee World Large Pharma, Pharmaceutical Public antibodies against a native antigen, without Alzheimer AD03 producing a systemic immune response. [CONT.] MimoVax™ Alzheimer's disease therapeutic - ProteoTech is developing an oral small molecule Exebryl-1® Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO USA ProteoTech Originator USA Biotechnology Private ProteoTech therapeutic (Exebryl-1®), targeting amyloid-beta (Abeta) protein fibrillogenesis, for the treatment of Alzheimer's disease (AD). In addition, Exebryl- 65 1® has been shown to reduce tau protein formation as well as exhibit anti-inflammatory properties such as astrocytosis and microgliosis. Tau protein inhibitors ProteoTech Owner USA Biotechnology Private [CONT.] Tasly Pharmaceutical Group Licensee China Pharmaceutical Private ANAVEX 2-73 Anavex Life Sciences is developing ANAVEX 2-73, ANAVEX 19-144 prodrug Calcium channel antagonists Alzheimer's disease (In volunteers) Phase I PO Germany ABX-CRO Collaborator Germany CRO Private a small molecule for the treatment of Alzheimer's disease (AD), epilepsy and stroke. The drug was developed using the company's proprietary SIGMACEPTOR™ platform. Various formulations 66 of the drug have been tested preclinically, but only the oral formulation is being assessed in ANAVEX2-73 Muscarinic M2 receptor antagonists Epilepsy (In volunteers) Phase I Unknown route Germany Anavex Life Sciences Originator Switzerland Biopharmaceutical Public clinical trials. A phase Ia single ascending dose Muscarinic M3 receptor antagonists Stroke (In volunteers) Phase I Unknown route Germany Anavex Life Sciences Owner Switzerland Biopharmaceutical Public trial of ANAVEX 2-73 in AD has been completed NMDA receptor antagonists Alzheimer's disease (Combination therapy) Preclinical Parenteral France Genesis Biopharma Collaborator Canada Biopharmaceutical Private in Germany [CONT.] Sigma-1 receptor agonists Alzheimer's disease (Monotherapy) Preclinical Parenteral Germany Sodium channel antagonists ARC 031 Archer Pharmaceuticals is developing ARC 031, a ARC 031SR Undefined mechanism Alzheimer's disease Phase I Unknown route USA Archer Pharmaceuticals Originator USA Pharmaceutical Private member of a new class of drugs known as soluble amyloid reducing/clearing agents (SARC), for the treatment of Alzheimer's disease. The parent 67 compound of this molecule is nilvadipine, a calcium channel blocker that is widely used in the treatment of hypertension (since 1991). Importantly, ARC 031 exerts its effect without ARC031 Archer Pharmaceuticals Owner USA Pharmaceutical Private calcium channel blocking. [CONT.] ARC031 SR ASP 0777 Astellas Pharma is developing ASP 0777 as a oral ASP0777 Undefined mechanism Alzheimer's disease Phase I PO USA Astellas Pharma US Originator USA Company treatment for dementia associated with 68 Alzheimer's disease. The mechanism of action for ASP 0777 has not been disclosed. Phase Ib development is underway in the US. Astellas Pharma US Owner USA Company AV 965 Avera Pharmaceuticals is developing the AV965 Serotonin 1A receptor antagonists Alzheimer's disease Phase I PO USA Avera Pharmaceuticals Originator Usa Pharmaceutical Private serotonin (5-HT)1A receptor antagonist AV 965 for schizophrenia-associated cognitive impairment 69 (cognition disorders) and Alzheimer's disease in the US. AV 965 was originated by Eli Lilly who licensed the drug and supporting intellectual property to Avera Pharmaceuticals in 2002. Cognition disorders Phase I PO USA Avera Pharmaceuticals Owner Usa Pharmaceutical Private [CONT.] AVN 322 Avineuro Pharmaceuticals (US) is developing the AVN-322 Serotonin 6 receptor antagonists Alzheimer's disease Phase I Unknown route USA Avineuro Pharmaceuticals Licensee World Pharmaceutical Private small molecule AVN 322, a serotonin 6 receptor antagonist, for the treatment of Alzheimer's 70 disease. The compound was in phase I development. Avineuro Pharmaceuticals licensed AVN 322 from ChemDiv Originator USA CRO Private ChemDiv. ChemDiv Owner USA CRO Private AZD 2184 AstraZeneca is developing AZD 2184 ([11C]AZD [11C]AZD 2184 Positron-emission tomography enhancers Alzheimer's disease (Diagnosis) Phase I IV Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public 2184) as an in vivo imaging agent for use in positron emission tomography (PET) in the diagnosis of Alzheimer's disease (AD). This 71 candidate 11C-radiolabelled, PET ligand selectively binds amyloid-beta (Abeta) peptides to enable visualisation of amyloid plaque deposits [11C]AZD2184 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public in the brain that are characteristic of AD. [CONT.] AZD2184 Navidea Biopharmaceuticals Licensee USA Biopharmaceutical Public AZD 2995 AstraZeneca is developing AZD 2995 ([11C]AZD [11C]AZD 2995 Positron-emission tomography enhancers Alzheimer's disease (Diagnosis) Phase I IV Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public 2995) as an in vivo imaging agent for use in positron emission tomography (PET) in the diagnosis of Alzheimer's disease (AD). This 72 candidate 11C-radiolabelled, PET ligand selectively binds amyloid-beta (Abeta) peptides to enable visualisation of amyloid plaque deposits [11C]AZD2995 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public in the brain that are characteristic of AD. [CONT.] AZD2995 Navidea Biopharmaceuticals Licensee USA Biopharmaceutical Public AZD 3293 AstraZeneca is developing AZD 3293, an orally AZD-3293 Amyloid precursor protein secretase inhibitors Alzheimer's disease Phase I PO USA Astex Pharmaceuticals Originator USA Pharmaceutical Public administered small-molecule for the treatment of Alzheimer's disease. AZD 3293 inhibits the amyloid precursor protein secretase, beta- secretase, which is a key protein involved in the 73 formation of myelin sheaths in peripheral nerve cells and in the pathogenesis of Alzheimer's disease. The enzyme inhibition prevents the build up of beta-amyloid to slow or stop the progression of the disease [CONT.] AZD3293 AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public BACE inhibitor - Janssen Pharmaceuticals and Shionogi are Amyloid precursor protein secretase inhibitors Alzheimer's disease (Early-stage disease) Phase I PO Europe Janssen Pharmaceuticals Licensee USA Pharmaceutical Public Janssen/Shionogi developing an oral beta-secretase (BACE; 74 amyloid precursor protein secretase) inhibitor for the treatment of prodromal (early-stage) Shionogi Originator Japan Large Pharma, Pharmaceutical Public Alzheimer's disease. A phase I trial is in progress Shionogi Owner Japan Large Pharma, Pharmaceutical Public in Europe. [CONT.] BACE1 protein inhibitor - Eli Eli Lilly is developing an inhibitor of beta 2434074 BACE1 protein inhibitors Alzheimer's disease Phase I PO Unknown Eli Lilly Originator USA Large Pharma, Pharmaceutical Public Lilly secretase (BACE1 protein) for the treatment of patients with Alzheimer's disease. The company aimed to design a molecule that could penetrate the blood-brain barrier and limit the formation of 75 beta-amyloid (Abeta)40/42 peptides. BACE1 protein catalyzes the first step of the two-step amyloid precursor protein (APP) cleavage LSN 2434074 Eli Lilly Owner USA Large Pharma, Pharmaceutical Public process, which in turn leads to the formation of LY 2434074 Abeta40/42 peptides [CONT.] LY-2434074 BACE1 protein inhibitor - A beta-amyloid converting enzyme (BACE1) BACE1 protein inhibitors Alzheimer's disease Phase I Unknown route USA Ligand Pharmaceuticals Owner USA Biotechnology Public Ligand/Merck inhibitor is in development with Merck and Ligand Pharmaceuticals for the treatment of Alzheimer's disease. A phase I multi-dose trial was completed in the US. According to Ligand's research 76 pipeline, the inhibitor compound is still in phase I development. BACE1 protein inhibitor - BACE1 protein inhibitors Ligand/Merck

76

The BACE1 enzyme is a key protein implicated in Merck & Co Collaborator USA Large Pharma, Pharmaceutical Public the pathogenesis of Alzheimer's disease. [CONT.]

Pharmacopeia Originator USA Biopharmaceutical Public BAY 858101 BAY 858101 is an IV-administered, 18F-labelled BAY85-8101 Undefined mechanism Alzheimer's disease (Diagnosis:Trial completed) Phase I IV Netherlands, Sweden Bayer HealthCare Pharmaceuticals Originator Germany Pharmaceutical Public radiopharmaceutical used with positron emission tomography (PET) for the diagnosis of disorders associated with neuroinflammation, including 77 multiple sclerosis and Alzheimer's disease. Piramal Healthcare acquired the programme from Bayer HealthCare Pharmaceuticals (formerly F-18 FEDAA1106 Multiple sclerosis (Diagnosis:Trial completed) Phase I IV Australia, Sweden Piramal Healthcare Owner World Pharmaceutical Public Bayer Schering Pharma). Two phase I clinical F18-FEDAA1106 trials have been completed. [CONT.] ZK 6032924 BIIB 037 Biogen Idec is developing BIIB 037, a fully BART Amyloid beta-protein inhibitors Alzheimer's disease Phase I IV USA Biogen Idec Licensee USA Large Pharma, Biotechnology Public human antibody against beta-amyloid, for the treatment of Alzheimer's disease. Phase I clinical development is underway in the US.

78 This lead candidate is a product of Biogen Idec BIIB037 Neurimmune Therapeutics Originator Switzerland Biotechnology Private and Neurimmune Therapeutics' neurodegenerative disease antibody research programme [see separate profile].

Neurimmune Therapeutics Owner Switzerland Biotechnology Private Bisnorcymserine Bisnorcymserine is an orally available, small Bisnorcymcerine Amyloid beta-protein precursor inhibitors Alzheimer's disease Phase I PO USA National Institute on Aging Originator USA Institution N/A molecule inhibitor of butyrylcholinesterase, an enzyme that appears to be elevated in amyloid- beta plaques in the brains of patients with 79 Alzheimer's disease (AD). Bisnorcymserine also acts to inhibit the formation of amyloid-beta precursor protein (Abeta-PP) in cell culture and in BNC Butyrylcholinesterase inhibitors Cognition disorders Preclinical PO USA National Institutes of Health (USA) Originator USA Institution N/A rats, which indicates potential for the prevention Poisoning Discontinued(Preclinical) PO USA QR Pharma Licensee World Biotechnology of the formation of amyloid plaques [CONT.] Raptor Pharmaceutical Corp Owner World Pharmaceutical Public BLU 8499 BELLUS Health (formerly known as Neurochem BLU8499 Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO Canada Asclepios Bioresearch (UK) Funder United Kingdom Investor Private Inc.) is developing a prodrug of tramiprosate, BLU 8499, for the treatment of Alzheimer's 80 disease. This agent increases brain exposure to tramiprosate, and is therefore expected to improve cognitive function and clinical outcomes. NRM-8499 GABA A receptor agonists BELLUS Health Originator Canada Biopharmaceutical Public A phase I trial has been completed in Canada. NRM8499 BELLUS Health Owner Canada Biopharmaceutical Public [CONT.] BMS 241027 Bristol-Myers Squibb is developing BMS 241027, BMS-241027 Tau protein inhibitors Alzheimer's disease Phase I IV USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public a small molecule, microtubule stabiliser for the treatment of Alzheimer's disease. The company's approach is to prevent the production of 81 abnormal tau protein, which is implicated in the decline in cognition of patients with Alzheimer's disease. Phase I development of BMS 240127 is underway in the US. Microtubule stabilizer Tubulin modulators Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

CTS 21166 CTS 21166 is a small molecule and orally ATG Z1 Amyloid precursor protein secretase inhibitors Alzheimer's disease Phase I IV USA Astellas Pharma Licensee World Large Pharma, Pharmaceutical Public bioavailable, amyloid precursor protein secretase (beta-secretase) inhibitor, which is being developed by CoMentis and its licensing partner, Astellas, as a disease-modifying treatment for 82 Alzheimer's disease (AD). In preclinical studies, CTS 21166 exhibits excellent efficacy, selectivity, brain penetration and pharmacological activity. The agent is in clinical development in the US. ATG-Z1 CoMentis Originator USA Biopharmaceutical Private [CONT.] CTS-21166 CoMentis Owner USA Biopharmaceutical Private DB 959 DB 959 is a highly selective, non- DB959 Peroxisome proliferator-activated receptor delta Alzheimer's disease (In volunteers) Phase I PO USA Bayer HealthCare Pharmaceuticals Originator USA Pharmaceutical Public thiazolidinedione, first-in-class dual peroxisome agonists proliferator activated receptor delta/gamma 83 (PPARdelta/gamma) agonist that has been acquired by T3D Therapeutics and will be DB959Na Peroxisome proliferator-activated receptor Dyslipidaemias (In volunteers) Discontinued(I) PO USA Bayer HealthCare Pharmaceuticals Owner USA Pharmaceutical Public developed as a once-daily oral therapy for gamma agonists Alzheimer's disease (AD) and other CNS T3D-959 Type 2 diabetes mellitus (In volunteers) Discontinued(I) PO USA T3D Therapeutics Licensee World Pharmaceutical Private disorders. [CONT.] DSP 8658 Dainippon Sumitomo Pharma and Sunovion DSP-8658 Peroxisome proliferator-activated receptor alpha Alzheimer's disease Phase I PO USA Dainippon Sumitomo Pharma Originator Japan Large Pharma, Pharmaceutical Public Pharmaceuticals are developing DSP 8658, an agonists orally active peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) 84 agonist, for the treatment of type 2 diabetes mellitus and Alzheimer's disease. DSP 8658 Peroxisome proliferator-activated receptor Type 2 diabetes mellitus Phase I PO USA Dainippon Sumitomo Pharma Owner Japan Large Pharma, Pharmaceutical Public emerged as a lead compound from Dainippon's gamma agonists research and development programme. [CONT.] Sunovion Pharmaceuticals Licensee USA Pharmaceutical Public DWP 09031 DWP 09031 is an orally administered, small DWP09031 Amyloid beta-protein inhibitors Alzheimer's disease (In volunteers) Phase I PO South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public molecule inhibitor of amyloid beta (Abeta) protein aggregation, being developed by Daewoong 85 Pharmaceutical for the treatment of Alzheimer's disease. Phase I clinical development is underway in South Korea.

DWP 09031 is available for licensing. Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public E 2012 E 2012 is an orally available, amyloid precursor E-2012 Amyloid precursor protein secretase modulators Alzheimer's disease (In volunteers:Trial completed) Phase I PO USA Eisai Co Ltd Originator Japan Large Pharma, Pharmaceutical Public protein secretase (gamma-secretase) modulator that is being developed by Eisai for the treatment of Alzheimer's disease (AD). It was discovered from the derivatives of seed compounds from Eisai's compound library using multi-dimensional analysis. The protease gamma-secretase cleaves 86 the amyloid precursor protein (APP) to produce amyloid-beta (Abeta) protein, a major component of AD-related plaques in the brain causing impaired neural function. E 2012 is undergoing clinical development for AD in the US. [CONT.] E2012 Eisai Co Ltd Owner Japan Large Pharma, Pharmaceutical Public E 2212 Eisai is developing an amyloid precursor protein E-2212 Amyloid precursor protein secretase modulators Alzheimer's disease (In volunteers) Phase I PO USA Eisai Inc Originator USA Pharmaceutical Public secretase modulator, E 2212, for the treatment of Alzheimer's disease (AD). The company has completed a US-based, E2212 Eisai Inc Owner USA Pharmaceutical Public randomised, double-blind, placebo-controlled, 87 single ascending dose phase I trial, which investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of E 2212 in 60 healthy subjects (NCT012212590)

E 2609 Eisai is developing E 2609, a beta-secretase-1 E2609 BACE1 protein inhibitors Alzheimer's disease Phase I PO USA Eisai Inc Originator USA Pharmaceutical Public (BACE 1) inhibitor, for the treatment of Alzheimer's disease (AD). The drug reduced total 88 beta-amyloid, resulting in symptomatic improvement as well as disease modification. Eisai Inc Owner USA Pharmaceutical Public Phase I development is underway in the US. GE Healthcare Collaborator United Kingdom Technology provider Public [CONT.] Encapsulated cell therapy - NsGene A/S is developing a cell therapy product ECB-AD Neuron stimulants Alzheimer's disease Phase I Intracerebral Sweden NsGene Originator Denmark Biotechnology Private Alzheimers's disease - NsGene for the treatment of Alzheimer's disease. The cell therapy product is based on human retinal pigment epithelial parent cell line (NGC-0295) 89 obtained from the organ donor that has been genetically modified to stably secrete human ECT-AD NsGene Owner Denmark Biotechnology Private nerve growth factor (NGF) and encapsulated in ECT-NGF the polyvinylalcohol cylindrical matrix. [CONT.] Encapsulated cell therapy - NsGene A/S is developing a cell therapy product Neuron stimulants Alzheimers's disease - NsGene for the treatment of Alzheimer's disease. The cell therapy product is based on human retinal pigment epithelial parent cell line (NGC-0295) 89 obtained from the organ donor that has been genetically modified to stably secrete human nerve growth factor (NGF) and encapsulated in the polyvinylalcohol cylindrical matrix. [CONT.] NsG0202 GSK 2647544 GlaxoSmithKline is developing oral lipoprotein- GSK-2647544 Phospholipase A2 inhibitors Alzheimer's disease (In volunteers) Phase I PO Australia GlaxoSmithKline Originator United Kingdom Large Pharma, Pharmaceutical Public associated phospholiapse A2 (Lp-PLA2) inhibitor, 90 GSK 2647544, for the treatment of Alzheimer's disease. A phase I trial was completed in GSK2647544 GlaxoSmithKline Owner United Kingdom Large Pharma, Pharmaceutical Public Australia. HPP 854 High Point Pharmaceuticals (a spin-off company HPP854 BACE1 protein inhibitors Alzheimer's disease Phase I PO USA High Point Pharmaceuticals Owner World Pharmaceutical Private from TransTech Pharma) is developing HPP 854, an orally active, small molecule compound that inhibits BACE1, the enzyme responsible for amyloid-beta (Abeta) generation, for potential 91 use in the treatment of Alzheimer's disease. BACE (beta-site amyloid precursor protein- cleaving enzyme) is a type-1 transmembrane TTP 854 TransTech Pharma Originator USA Pharmaceutical Private protein and an aspartyl protease with beta- TTP-854 secretase activity [CONT.] TTP854 Huperzine A - Neuro-Hitech/Xel Neuro-Hitech and Xel Pharmaceuticals is HupA transdermal Acetylcholinesterase inhibitors Alzheimer's disease Phase I Transdermal China Mayo Clinic Originator USA Institution N/A developing huperzine A in transdermal patch (XEL 001HP) and topical gel (XEL 001HG) formulations, using Xel's drug delivery 92 technology, for the treatment of Alzheimer's Qian ceng ta transdermal Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Topical USA Mayo Clinic Owner USA Institution N/A disease (AD). Phase I development of the patch Qian-ceng-ta transdermal Antioxidants Alzheimer's disease Preclinical Transdermal USA Neuro-Hitech Licensee World Pharmaceutical Public formulation is underway in China and an IND XEL 001HG NMDA receptor antagonists Xel Pharmaceuticals Collaborator USA Pharmaceutical Private filing is expected in the US soon. Preclinical XEL 001HP Xel Pharmaceuticals Technology Provider USA Pharmaceutical Private development of the gel formulation is underway Xiangxue Pharmaceutical Collaborator China Pharmaceutical JNJ 54861911 Janssenin the US. Research [CONT.] & Development is developing JNJ-54861911 Undefined mechanism Alzheimer's disease (In volunteers) Phase I PO Belgium Janssen Research & Development Originator USA Pharmaceutical Public JNJ 54861911 for the oral treatment of Alzheimer's disease. Phase I clinical development in healthy volunteers is in progress in Belgium.

93 In May 2013, Janssen Research & Development Janssen Research & Development Owner USA Pharmaceutical Public initiated a phase I clinical trial to evaluate the safety, tolerability and pharmacodynamics of multiple ascending oral doses of JNJ 54861911 in healthy elderly volunteers (NCT01887535) [CONT.] KU 046 Kareus Therapeutics is developing KU 046 for the KU-046 Amyloid beta-protein modulators Alzheimer's disease (In volunteers) Phase I PO USA Kareus Therapeutics Originator Switzerland Pharmaceutical Private treatment of Alzheimer's disease. The compound was discovered using Kareus' bioenergetics and Karlect chemistry platforms, which combines currently marketed drugs and GRAS molecules to 94 produce proprietary chemical entities that have an improved therapeutic index. KU 046 targets pathways upstream of amyloid beta peptide production and significantly improved cognition in a number of preclinical models [CONT.] Kareus Therapeutics Owner Switzerland Pharmaceutical Private LY 3002813 Eli Lilly is developing LY 3002813, a biological LY3002183-SC Undefined mechanism Alzheimer's disease Phase I IV Japan, USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public agent for the treatment of Alzheimer's disease. A phase I clinical trial of intravenous and subcutaneous formulations is underway in the US and Japan.

In May 2013, Eli Lilly initiated a randomised, LY3002813 Alzheimer's disease Phase I SC Japan, USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public 95 double-blind, placebo-controlled phase I trial to investigate the safety, tolerability and pharmacokinetics of LY 3002813 in patients with mild to moderate Alzheimer's disease (NCT01837641) [CONT.]

LY3002813-IV N3pG-Asz Monoclonal Antibody MCD 386 Mithridion is developing MCD 386, a highly CDD 0102 Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO USA Mithridion Licensee World Biopharmaceutical selective muscarinic M1 receptor agonist, for the CDD 0102J Muscarinic M1 receptor agonists Alzheimer's disease Preclinical Transdermal USA University of Toledo Originator USA University N/A treatment of Alzheimer's disease (AD) and CDD-0102 Progressive supranuclear palsy Preclinical PO USA University of Toledo Owner USA University N/A cognitive impairment in schizophrenia. This small CDD-0102-J Schizophrenia Preclinical PO USA molecule drug is designed to improve the brain 96 CDD-0102J Schizophrenia Preclinical Transdermal USA functions of memory and cognition, as well as to MCD-386 stop or delay AD-related pathology that cause MCD-386 Forte neuronal cell death. Phase I development of oral MCD-386 Forte/Transderm MCD 386 controlled release in AD is underway in MCD-386 Transderm the US [CONT.] MCD-386CR Mesenchymal stem cell therapy Medipost is developing a product (called Neurostem® Tissue replacements Alzheimer's disease Phase I Intracerebral South Korea Medipost Originator South Korea Biotechnology Private for neurological disorders - Neurostem®) based on adult mesenchymal stem Medipost cells (MSC) derived from umbilical cord blood for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and stroke, 97 via recovery of functionality and tissues of the CNS. The MSCs in Neurostem® are believed to promote proliferation and differentiation of neuro- progenitor cells within the host thereby restoring functionality of the tissue [CONT.] Neurostem®-AD Medipost Owner South Korea Biotechnology Private MK 3328 Merck is developing MK 3328, a fluoro- [18F]MK-3328 Alzheimer's disease (Diagnosis) Phase I IV Belgium Merck & Co Originator USA Large Pharma, Pharmaceutical Public azabenzoxazole compound, as a positron emission tomography (PET) tracer for the diagnosis of neurodegenerative disorders, including Alzheimer's disease. Phase I development is ongoing in Belgium. 98 The direct, non-invasive detection of beta- [18F]MK3328 Merck & Co Owner USA Large Pharma, Pharmaceutical Public amyloid (Abeta) plaque deposits using PET imaging is a promising method to accurately diagnose Alzheimer's disease (AD) prior to the onset of severe cognitive decline [CONT.]

MK-3328 MK3328 OSI 754 OSI 754 is an oral inhibitor of farnesyl CP 609754 Farnesyltranstransferase inhibitors Alzheimer's disease Phase I PO USA AstraZeneca Sub-licensee United Kingdom Large Pharma, Pharmaceutical Public transferase, an enzyme of crucial importance in the ras signalling pathway. This compound was originally developed by OSI Pharmaceuticals in 99 collaboration with Pfizer and subsequently licensed to Link Medicine Corporation for all LNK-754 Neurodegenerative disorders Phase I PO USA Link Medicine Corporation Licensee USA Pharmaceutical Private indications, excluding oncology. AstraZeneca Bladder cancer Discontinued(I) PO USA OSI Pharmaceuticals Originator USA Biotechnology Public have acquired the rights to this programme. OSI Pharmaceuticals Owner USA Biotechnology Public Pioglitazone companion Takeda is utilising Zinfandel Pharmaceuticals' AD4833/TOMM40 Alzheimer's disease (Diagnosis) Phase I Unknown route European Union, USA Takeda Originator Japan Large Pharma, Pharmaceutical Public diagnostic TOMM40 biomarker assay to identify high risk individuals as candidates for clinical trials investigating the use of pioglitazone for the prevention of Alzheimer's disease. The TOMM40 100 biomarker is associated with an increased risk of developing Alzheimer's disease, and this assay can be used to gauge which older individuals at high risk of disease onset should be enrolled in clinical trials [CONT.] Diagnostic tests Phase I Unknown route European Union, USA Zinfandel Pharmaceuticals Originator USA Biotechnology Private PQ 912 Probiodrug is developing PQ 912, an orally active PQ-912 Glutaminyl-peptide cyclotransferase inhibitors Alzheimer's disease (In volunteers) Phase I PO Switzerland Probiodrug Originator Germany Pharmaceutical Private small molecule, for the treatment of Alzheimer's disease. PQ 912 inhibits the enzymatic activity of glutaminyl-peptide cyclotransferase (glutaminyl 101 cyclase), a metalloenzyme that catalyses the formation of pyroglutamate-modified amyloid- beta, a highly toxic amyloid-b.eta variant that is involved in the development and progression of Alzheimer's disease [CONT.] PQ 912 Probiodrug is developing PQ 912, an orally active Glutaminyl-peptide cyclotransferase inhibitors small molecule, for the treatment of Alzheimer's disease. PQ 912 inhibits the enzymatic activity of glutaminyl-peptide cyclotransferase (glutaminyl 101 cyclase), a metalloenzyme that catalyses the formation of pyroglutamate-modified amyloid- beta, a highly toxic amyloid-b.eta variant that is involved in the development and progression of Alzheimer's disease [CONT.] PQ912 Probiodrug Owner Germany Pharmaceutical Private PRX 07034 PRX 07034, a small-molecule serotonin 6 (5-HT6) PRX-07034 Serotonin 6 receptor antagonists Alzheimer's disease Phase I PO USA EPIX Pharmaceuticals Originator USA Biopharmaceutical Public receptor antagonist, is in development for the treatment of Alzheimer's disease, obesity and cognitive impairment associated with 102 schizophrenia. The compound was originally in development with EPIX Pharmaceuticals. However, rights to the the compound have been Cognition disorders Phase I PO USA Unknown Owner USA Company sold to an undisclosed company. [CONT.] Obesity Phase I PO USA R 1500 R 1500, an enzyme inhibitor, in clinical R-1500 Enzyme inhibitors Alzheimer's disease Phase I Unknown route Europe Roche Originator Switzerland Large Pharma, Pharmaceutical Public 103 development with Roche for the potential treatment of Alzheimer's disease in Europe. R1500 Roche Owner Switzerland Large Pharma, Pharmaceutical Public R 1577 Roche is developing R 1577, an enzyme inhibitor, R-1577 Enzyme inhibitors Alzheimer's disease Phase I PO Europe Roche Originator Switzerland Large Pharma, Pharmaceutical Public 104 for potential utility in the treatment of Alzheimer's disease in Europe R1577 Roche Owner Switzerland Large Pharma, Pharmaceutical Public RG 7129 Roche is developing RG 7129, an orally RG7129 BACE1 protein inhibitors Alzheimer's disease (In volunteers) Phase I PO France, USA Roche Originator Switzerland Large Pharma, Pharmaceutical Public administered inhibitor of beta-secretase (BACE- 105 1), for the treatment of Alzheimer's disease. RG 7129 is undergoing phase I clinical development RO 5508887 Roche Owner Switzerland Large Pharma, Pharmaceutical Public in the US and France. RO5508887 RQ 00000009 RaQualia is developing RQ 00000009, an oral, RQ-00000009 Acetylcholine stimulants Alzheimer's disease Phase I PO Japan Pfizer Originator USA Large Pharma, Pharmaceutical Public small molecule serotonin 4 receptor (5-HT4) partial agonist, for the treatment of Alzheimer's disease (AD). RQ 00000009 is designed to 106 improve memory and cognitive function by increasing acetylcholine secretion, and also modify the pathophysiological condition of AD by decreasing amyloid beta-protein production. RQ-9 Amyloid beta-protein inhibitors Pfizer Owner USA Large Pharma, Pharmaceutical Public [CONT.] RQ9 Serotonin 4 receptor agonists RaQualia Pharma Licensee World Pharmaceutical Private S 47445 Les Laboratories Servier (Servier) is developing S CX 1632 AMPA receptor agonists Alzheimer's disease Phase I Unknown route France Cortex Pharmaceuticals Originator USA Pharmaceutical Public 47445 for the treatment of neurodegenerative disorders. S 47445 is an AMPA receptor agonist, which was developed using Cortex's Ampakine® technology and was later licensed to Servier under a research collaboration and license 107 agreement between the two companies. Servier originally had the rights to develop three of Cortex's Ampakine® compounds under the licensing agreement, but it discontinued development of the other two in favour of S CX1632 Nerve growth factor stimulants Dementia Phase I Unknown route France Cortex Pharmaceuticals Owner USA Pharmaceutical Public 47445. Phase I development of S 47445 is S47445 Mild cognitive impairment Phase I Unknown route France Servier Licensee World Pharmaceutical Private underway in France. [CONT.] University of California at Irvine Technology Provider USA University N/A SAR 228810 Sanofi is developing SAR 228810 for the Anti-protofibrillar AB mAb Amyloid inhibitors Alzheimer's disease Phase I IV Sweden Sanofi Originator France Large Pharma, Pharmaceutical Public treatment of Alzheimer's disease. It is a monoclonal antibody that inhibits amyloid 108 fibrillogenesis. The company has described the drug as an 'anti-protofibrillar AB mAb'. Phase I development of intravenous and subcutaneous formulations is underway in Sweden. SAR228810 Alzheimer's disease Phase I SC Sweden Sanofi Owner France Large Pharma, Pharmaceutical Public sGC 1061 sGC 1061 is a lead compound from a new class of Nitric oxide mimetic (sGC-1061) Amyloid beta-protein inhibitors Alzheimer's disease Phase I Unknown route USA Alzheimers Drug Discovery Foundation Funder USA Company compounds, called nomethiazoles (or NO-chimera prodrugs), which is in development with sGC Pharma as a potential therapy for Alzheimer's disease (AD) and age-related cognitive 109 impairment (memory disorders). The nomethiazoles therapeutic class was initially defined by Professor Greg Thatcher while at Nomethiazoles (NO-chimera prodrugs) - sGC Nitric oxide stimulants Alzheimer's disease Preclinical Unknown route USA Queens University Originator Canada University N/A Queen's University; he subsequently went to Pharma work at the University of Illinois College of sGC-1061 Tau protein inhibitors sGC Pharma Licensee USA Biotechnology Pharmacy [CONT.] Sustained-release sGC-1061 University of Illinois Originator USA University N/A SUVN 502 Suven Life Sciences is developing an oral M1 Serotonin 6 receptor antagonists Alzheimer's disease Phase I PO Switzerland Suven Life Sciences Originator India Company formulation of SUVN 502, a selective serotonin 6 (5-HT6) receptor antagonist, for the symptomatic treatment of Alzheimer's disease, and other 110 M1 of SUVN-502 Attention-deficit hyperactivity disorder Phase I PO Switzerland Suven Life Sciences Owner India Company disorders of memory and cognition such as Cognition disorders Phase I PO Switzerland schizophrenia, Parkinson's disease and attention Parkinson's disease Phase I PO Switzerland deficit hyperactivity disorder (ADHD). [CONT.] Schizophrenia Phase I PO Switzerland TAK 070 The University of Tokyo is developing TAK 070 for TAK-070 BACE1 protein inhibitors Alzheimer's disease (In the elderly, In volunteers) Phase I PO Japan Takeda Originator Japan Large Pharma, Pharmaceutical Public the treatment of Alzheimer's disease (AD). This orally active, non-peptidic human beta secretase (beta-secretase, BACE) inhibitor was discovered 111 by Takeda. The company had conducted preclinical development for AD in Japan, prior to licensing the compound to the University of TAK070 Takeda Owner Japan Large Pharma, Pharmaceutical Public Tokyo. [CONT.] University of Tokyo Licensee Japan University N/A TD 8954 Theravance is developing a CNS-penetrant TD-8954 Serotonin 4 receptor agonists Alzheimer's disease Phase I Unknown route USA Theravance Originator USA Biopharmaceutical Public serotonin 4 receptor (5-HT4) agonist, TD 8954, to ameliorate the cognitive impairment associated with Alzheimer's disease (AD). Serotonin 4 112 receptors are widely expressed in the hippocampus, amygdala and prefrontal cortex, all of which receive substantial cholinergic input, and are involved in cognition. [CONT.] Gastrointestinal disorders Phase I Unknown route USA Theravance Owner USA Biopharmaceutical Public TTP 4000 TTP 4000 is a large molecule fusion between the TTP4000 Advanced glycosylation end product inhibitors Alzheimer's disease Phase I SC USA Pfizer Licensee World Large Pharma, Pharmaceutical Public ligand binding domains of an extracellular portion of the advanced glycation end product receptor (RAGE) and immunoglobulin G under development with TransTech Pharma as a 113 treatment for Alzheimer's disease. RAGE has been identified as a receptor for amyloid-beta and other amyloidogenic proteins including serum amyloid A and amylin, which play a critical role in the pathophysiology of Alzheimer's disease TransTech Pharma Originator USA Pharmaceutical Private [CONT.] TransTech Pharma Owner USA Pharmaceutical Private UB 311 United Biomedical (UBI) is developing UB 311, a UBITh AD immunotherapeutic vaccine (UB 311) - Amyloid beta-protein inhibitors Alzheimer's disease Phase I IM Taiwan, USA United Biomedical Originator USA Biopharmaceutical Private liquid intramuscular delivered amyloid beta United Biomedical 114 protein inhibitor vaccine, for the treatment of mild-to-moderate Alzheimer's disease. Phase I development is underway in Taiwan and the US. United Biomedical Owner USA Biopharmaceutical Private V 950 V 950 is a vaccine product that is being V-950 Immunostimulants Alzheimer's disease Phase I IM USA CSL Technology Provider Australia Large Pharma, Biopharmaceutical Public developed by Merck & Co. for the treatment of Alzheimer's disease (AD). Merck is developing a preparation of V 950 using Iscomatrix® adjuvant 115 technology in-licensed from CSL. This adjuvant is expected to improve Merck's vaccine by producing more potent and durable immune V950 Merck & Co Originator USA Large Pharma, Pharmaceutical Public responses against certain AD antigens. [CONT.] Merck & Co Owner USA Large Pharma, Pharmaceutical Public