Alzheimer's Disease (Preclinical & Research) Drug Development Phase Organisations Drug Introduction Synonyms Mechanism Of Action Indication Phase Route Country Name Role Country Type Ownership IRX 4204 IRX 4204 is an orally bioavailable, first in class, AGN 194204 Retinoid X receptor agonists Prostate cancer Phase II PO USA Allergan Originator USA Large Pharma, Pharmaceutical Public retinoid X receptor (RXR; rexinoid) agonist being AGN-194204 Alzheimer's disease Preclinical PO USA Io Therapeutics Owner World Biopharmaceutical Private developed by Io Therapeutics. The initial focus is AGN194204 Parkinson's disease Preclinical PO USA Mount Sinai School of Medicine Collaborator USA University N/A for the treatment of castration-resistant prostate ALRT 4204 The Michael J. Fox Foundation for Parkinsons Research Collaborator USA Institution N/A cancer, but may also be developed for non-small cell lung cancer. IRX 4204 demonstrated activity ALRT-4204 against a variety of human cancers in vitro and ALRT4204 in animal models, including prostate, breast, IRX-4204 1 pancreatic, and lung [CONT.] IRX4204 NRX 194204 NRX 4204 NRX-194204 NRX-4204 NRX194204 NRX4204 VTP 194204 VTP-194204 VTP194204 Stem cell therapies - RNL BIO RNL BIO (South Korea) is researching and Adipose stem cell therapies - RNL BIO Cell replacements Facial hemiatrophy Phase II Parenteral South Korea Asan Medical Center Collaborator South Korea Hospital N/A developing stem cell therapies derived from adult Adult-derived stem cell therapies - RNL BIO Osteoarthritis Phase II Intra articular South Korea RNL BIO Originator South Korea Biotechnology sources, such as cord blood, placenta, hair Astrostem Thromboangiitis obliterans Phase II Parenteral South Korea RNL BIO Owner South Korea Biotechnology follicle and adipose (fat) tissue. The company is Autologous adipose stem cells - RNL BIO Intervertebral disc degeneration I/II Parenteral South Korea RST Biomedikal Sanayi Licensee Turkey Biotechnology focussing on the development of mesenchymal Cancerstem Osteonecrosis I/II Parenteral South Korea University of Newcastle upon Tyne Collaborator United Kingdom University N/A stem cell therapies derived from adipose fat. Clinical development is underway in Fat-derived stem cell therapies - RNL BIO Spinal cord injuries I/II Intraspinal South Korea osteonecrosis, interverterbral disc degeneration, Lipostem-DM Spinal cord injuries I/II Intrathecal South Korea 2 osteoarthritis, thromboangiitis obliterans, facial Lipostem-Femoran Spinal cord injuries I/II IV South Korea hemiatrophy, liver disorders, and spinal cord Mesenchymal stem cell therapies - RNL BIO Liver disorders Clinical IV Asia injury [CONT.] RNL-Astrostem™ Alzheimer's disease Preclinical IV South Korea RNL-JointStem® Cancer Preclinical Parenteral South Korea Vascostem™ Cerebral infarction Preclinical Parenteral South Korea Diabetes mellitus Preclinical Parenteral South Korea Fracture Preclinical Parenteral South Korea Ischaemic heart disorders Preclinical Intraventricular South Korea Adult neural stem cell therapy - StemCells is developing an adult neural stem cell hCNS-SC Cell replacements Age-related macular degeneration I/II Intraocular USA Oregon Health & Science University Collaborator USA University N/A StemCells therapy, known as HuCNS-SC®, for the treatment of disorders in all three regions of the HuCNS-SC Spinal cord injuries I/II Intraosseous Switzerland ReNeuron Technology Provider United Kingdom Biopharmaceutical Public CNS (brain, spinal cord, eyes). Researchers at 3 StemCells have succeeded in purifying stem cells HuCNS-SC cells Pelizaeus-Merzbacher disease Phase I Intracerebral USA StemCells Originator USA Biotechnology Public away from other cells in brain tissue by using HuCNS-SC® Alzheimer's disease Preclinical Parenteral USA StemCells Owner USA Biotechnology Public specific stem cell markers combined with state-of- Neurodegenerative disorders stem cell therapy - Stroke Preclinical Parenteral USA University of California at Irvine Collaborator USA University N/A the-art cell sorting. [CONT.] StemCells Neuronal ceroid lipofuscinosis Discontinued(I) Intracerebral USA Gene therapies - ReGenX Biosciences ReGenX Biosciences is developing personalised NAV™ therapeutics - ReGenX Biosciences Gene transference Haemophilia B I/II IV USA ARIAD Pharmaceuticals Collaborator USA Pharmaceutical Public gene therapies for eye, neurodegenerative, Neuronal ceroid lipofuscinosis Phase I Intracranial USA ARIAD Pharmaceuticals Technology Provider USA Pharmaceutical Public haematological and metabolic disorders, using its Age-related macular degeneration Preclinical Ophthalmic USA ReGenX Biosciences Originator USA Biopharmaceutical NAV™ gene delivery technology. NAV™ includes Alzheimer's disease Preclinical Parenteral USA ReGenX Biosciences Owner USA Biopharmaceutical a range of proprietary recombinant adeno- Haemophilia A Preclinical Parenteral USA St. Jude Childrens Research Hospital Collaborator USA Hospital N/A associated viral (rAAV) vectors, including rAAV7, Hypercholesterolaemia Preclinical Parenteral USA University of Pennsylvania Medical Center Collaborator USA University N/A 4 rAAV8, rAAV9 and rAAVrh10. [CONT.] Leber congenital amaurosis Preclinical Ophthalmic USA Weill Cornell Medical College Collaborator USA University N/A Metachromatic leukodystrophy Preclinical Intracranial USA Mucopolysaccharidosis I Preclinical Parenteral USA Mucopolysaccharidosis III Preclinical Intracranial USA Mucopolysaccharidosis VI Preclinical Parenteral USA Retinitis pigmentosa Preclinical Ophthalmic USA RNS 60 RNS 60 is a charge-stabilised nanostructure RNS-60 G protein-coupled receptor modulators Asthma (Combination therapy) I/II Inhalation USA Revalesio Originator USA Biotechnology Private (CSN) product that is in development with the biotechnology company Revalesio for the treatment of asthma and other neurological inflammatory disorders. CSNs are aqueous-based nano-bubble cores surrounded by a stable 5 molecular scaffolding that could alter whole cell conductance through effects on voltage-gated ion channels and other voltage-sensing proteins, and RNS60 Ion channel modulators Asthma Phase I IV USA Revalesio Owner USA Biotechnology Private thereby modulating the expression of G-protein Myocardial infarction (In volunteers) Phase I IV USA Rush University Collaborator USA University N/A coupled receptors and secretion of cytokines, Alzheimer's disease Preclinical Unknown route USA chemokines and adhesion molecules [CONT.] Multiple sclerosis Preclinical IV USA Parkinson's disease Preclinical Unknown route USA Zinc monocysteine Synthetic Biologics (formerly Adeona AEN 100 Antioxidants Amyotrophic lateral sclerosis I/II PO USA Adeona Pharmaceuticals Originator USA Biotechnology Public Pharmaceuticals) is developing zinc-based therapeutics, including a proprietary formulation of orally available zinc monocysteine, for the treatment of Alzheimer's disease and 6 amyotrophic lateral sclerosis (ALS). The product was originally developed as a prescription medical food; however, following positive results AEN-100 Free radical scavengers Alzheimer's disease Preclinical PO USA Synthetic Biologics Owner USA Biotechnology Public from a 42 patient clinical study, the company AEN-100/AEN-200 Glutathione peroxidase stimulants now plans to develop the product as a reaZin™ prescription pharmaceutical [CONT.] Zinc cysteine - Adeona Neurological disorder stem cell Neuralstem is developing neural stem cells from Adult neural stem cells - Neuralstem Cell replacements Amyotrophic lateral sclerosis Phase I Intraspinal USA China Medical University Hospital Collaborator Taiwan Hospital N/A therapies - Neuralstem the human brain and spinal cord for the HNSC Alzheimer's disease Preclinical Unknown route USA CJ Cheiljedang Corp. Collaborator South Korea Biopharmaceutical treatment of a range of neurological disorders, HSSC Amyotrophic lateral sclerosis Preclinical Intraspinal Taiwan Emory University Collaborator USA University N/A including amyotrophic lateral sclerosis (ALS), NSI 566 Brain injuries Preclinical Unknown route USA Neuralstem Originator Usa Company Huntington's disease, ischaemic spastic NSI 566RSC Cerebral palsy Preclinical Unknown route USA Neuralstem Owner Usa Company paraplegia, stroke and traumatic spinal cord NSI-566 Diabetic neuropathies Preclinical Unknown route USA University of California, San Diego Technology Provider USA University N/A injuries. The company's patent-protected NSI-566RSC Huntington's disease Preclinical Unknown route Germany University of Freiburg Collaborator Germany University N/A 7 technology is used to control the differentiation NSI566 Lysosomal storage diseases Preclinical Unknown route USA of the stem cells into mature physiologically Multiple sclerosis Preclinical Unknown route USA relevant human neurons and glia, and to produce Optic neuritis Preclinical Unknown route USA commercial quantities of these cells [CONT.] Paraplegia Preclinical Unknown route USA Parkinson's disease Preclinical Unknown route USA Spinal cord injuries Preclinical Intraspinal South Korea, USA Stroke Preclinical Intracerebral China, USA NSI 189 Neuralstem is developing NSI 189, an orally NSI-189 Neurogenesis stimulants Major depressive disorder Phase I PO USA Neuralstem Originator Usa Company active, first-in-class, small molecule neurogenic therapeutic for the treatment of major depressive disorder. The compound can cross the blood- NSI-189 phosphate Alzheimer's disease Preclinical PO USA Neuralstem Owner Usa Company 8 brain barrier and appears to have the effect of NSI189 Brain injuries Preclinical Unknown route USA Summit Pharmaceuticals International Corporation Licensee Japan Company stimulating neurogenesis in the hippocampus by Cognition disorders Preclinical PO USA "recruiting" the patient's own neural stem cells to Neurodegenerative disorders Preclinical PO USA repair or protect against CNS damage. [CONT.] Post-traumatic stress disorders Preclinical PO USA Stroke Preclinical Unknown route USA TT 301 Transition Therapeutics is developing TT 301, a TT301 Cytokine inhibitors CNS disorders (In volunteers) Phase I IV Canada, USA Northwestern University Originator USA University N/A small molecule compound that inhibits the overproduction of inflammatory cytokines, such as interleukin-1 beta and tumour necrosis factor 9 alpha, for the treatment of central nervous system indications such as intracerebral haemorrhage and traumatic brain injury. [CONT.] Alzheimer's disease Preclinical PO Canada Northwestern University Owner USA University N/A Rheumatoid arthritis Preclinical PO Canada Transition Therapeutics Licensee Canada Biopharmaceutical Public VBY 036 Virobay is developing a selective small-molecule VBY-036 Cathepsin S inhibitors Neuropathic pain (In volunteers) Phase I PO USA Virobay Originator USA Pharmaceutical Private cathepsin S inhibitor, VBY 036, as an oral treatment for neuropathic pain and Alzheimer's disease. ViroBay proposes that the drug is first-in- 10 class with its therapeutic approach, and that the drug is suitable for once-daily dosing. Early research is underway for Alzheimer's disease and phase I clinical development is underway for neuropathic pain in the US. [CONT.] Alzheimer's disease Research PO USA Virobay Owner USA Pharmaceutical Private Research programme: protease Virobay in the US has a research programme VBY 106 Cathepsin B inhibitors Autoimmune disorders 0 PO USA Virobay Originator USA Pharmaceutical Private inhibitors - Virobay developing small-molecule protease inhibitors for the treatment of Alzheimer's disease, autoimmune diseases, bone cancer, hepatic fibrosis, neuropathic pain and cancer. The 11 company has developed HCV protease inhibitors and cathepsin inhibitors. Development has VBY 285 Cathepsin inhibitors Bone cancer 0 Unknown route USA Virobay Owner USA Pharmaceutical Private reached phase 0 development in autoimmune VBY 825 Cathepsin S inhibitors Neuropathic pain 0 PO USA disorders, bone cancer and neuropathic pain, and VBY-106 Hepatitis C protease inhibitors Alzheimer's disease Research PO USA early research is being conducted in Alzheimer's VBY-285 Cancer pain Discontinued(Preclinical) PO USA disease [CONT.] VBY-825 Hepatitis C Discontinued(Preclinical) PO USA AZD 3102 AZD 3102 is a human monoclonal antibody with AZD-3102 Undefined mechanism Alzheimer's disease Preclinical Parenteral Europe, USA AstraZeneca Licensee World Large Pharma, Pharmaceutical Public high affinity for an undisclosed Alzheimer's disease (AD) target. The antibody is being 12 developed by AstraZeneca in collaboration with Dyax, and could have utility in the modification of AD progression. Preclinical development is AZD3102 Dyax Originator USA Biopharmaceutical Public underway in the US and Europe. Dyax Owner USA Biopharmaceutical Public AZD 6319 AstraZeneca is developing AZD 6319, a selective AZD-6319 Nicotinic receptor agonists Alzheimer's disease Preclinical IM USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public alpha7 nicotinic receptor (NNR) agonist for the treatment of Alzheimer's disease (AD). Studies have shown that selective acute alpha7 NNR stimulation has delayed effects on the neural 13 systems engaged in spatial working memory; delayed, persistent improvements in cognition may indicate a long-term alteration in synaptic efficacy and/or receptor signalling in working memory circuitry [CONT.] AZD6319 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

Bexarotene - ReXceptor ReXceptor is developing bexarotene as a Peroxisome proliferator-activated receptor Alzheimer's disease Preclinical PO USA Alzheimers Drug Discovery Foundation Funder USA Company treatment for Alzheimer's disease (AD). agonists Preclinical development is underway in the US.

The drug was originated by Ligand Protein synthesis inhibitors BrightFocus Foundation Funder USA Investor Pharmaceuticals and is available in both oral and 14 topical formulations for the treatment of cutaneous T-cell lymphoma in the US, Europe, Bolivia and Chile [see separate profiles]. [CONT.]

Retinoic acid receptor agonists Case Western Reserve University Technology Provider USA University N/A Retinoid X receptor agonists Ligand Pharmaceuticals Originator USA Biotechnology Public ReXceptor Owner USA Biopharmaceutical Memoquin Lay Line Genomics is developing memoquin, a Undefined mechanism Alzheimer's disease Preclinical PO Italy Lay Line Genomics Market Licensee World Biopharmaceutical Private low molecular weight molecule based on a chemical scaffold able to support multiple pharmacophores, as a potential therapeutic for 15 Alzheimer's disease. It has been developed with the aim of obtaining a multifunctional molecule effective on different biochemical cascades, University of Bologna Originator Italy University N/A relevant for Alzheimer's-like pathology. [CONT.] University of Bologna Owner Italy University N/A MK 7622 Merck is developing MK 7622, a small-molecule MK-7622 Alzheimer's disease (Adjunctive treatment:Adjunct to Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public quinazolinone compound, as a potential therapy donepezil) for Alzheimer's disease (AD). A phase IIb trial (MK-7622-012 AM1) is planned in the US to 16 assess the efficacy and tolerability of different doses of MK 7622 capsules (5mg, 15mg or 45mg once daily) as an adjunct to donepezil in patients with mild-to-moderate AD Merck & Co Owner USA Large Pharma, Pharmaceutical Public (NCT01852110). [CONT.] NC 1900 Japan-based pharmaceutical company Nippon- NC-1900 Undefined mechanism Alzheimer's disease Preclinical Injection Japan Nippon Chemiphar Originator Japan Pharmaceutical Public Chemiphar is developing the active-fragment analogue of arginine-vasopressin, NC 1900, for 17 the potential treatment of Alzheimer's disease. The drug has also been investigated in a NC1900 Alzheimer's disease Preclinical Inhalation USA Nippon Chemiphar Owner Japan Pharmaceutical Public preclinical model of schizophrenia. [CONT.] Schizophrenia Preclinical Injection Japan NXD 1191 NXD 1191, a spheron targeting agent, is NXD-1191 Alzheimer's disease Preclinical Unknown route Canada Nymox Pharmaceutical Corporation Originator Canada Biopharmaceutical Public undergoing preclinical investigation with Nymox Pharmaceutical Corporation in Canada for its potential to inhibit the formation of senile plaques from spherons and as a therapeutic for patients 18 with Alzheimer's disease (AD).

Spherons, a brain entity discovered by Nymox Spheron targeting drug Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public researchers, are tiny balls of densely packed protein found in brain cells. [CONT.]

NXD 3109 NXD 3109, a spheron targeting agent, is in NXD-3109 Alzheimer's disease Preclinical Unknown route Canada Nymox Pharmaceutical Corporation Originator Canada Biopharmaceutical Public preclinical development with Nymox Pharmaceutical Corporation in Canada for its potential to inhibit the formation of senile plaques from spherons and as a potential therapeutic for 19 Alzheimer's disease (AD).

Spherons, a brain entity discovered by Nymox Spheron targeting agents Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public researchers, are tiny balls of densely packed protein found in brain cells. [CONT.]

NXD 9062 Nymox Pharmaceutical Corporation is NXD-9062 Undefined mechanism Alzheimer's disease Preclinical Unknown route Canada Nymox Pharmaceutical Corporation Originator Canada Biopharmaceutical Public preclinically developing NXD 9062 as a potential treatment for Alzheimer's disease (AD) in 20 Canada. NXD 9062 works by inhibiting cell damage similar to that found in the AD brain. The agent is undergoing further preclinical NXD9062 Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public development in Canada. Phenserine Phenserine is a phenylcarbamate analogue of DWJ301 Acetylcholinesterase inhibitors Alzheimer's disease Preclinical PO South Korea Cenomed BioSciences Sub-licensee World Biopharmaceutical Private physostigmine and a selective acetylcholinesterase inhibitor that is being developed for the teatment of poisoning following 21 Phenserine tartrate Amyloid beta-protein precursor inhibitors Poisoning Preclinical PO USA Daewoong Pharmaceutical Sub-licensee South Korea Pharmaceutical Public exposure to organophosphorous nerve agents Alzheimer's disease Discontinued(Clinical) PO USA National Institute on Aging Originator USA Institution N/A and Alzheimer's disease (AD). The compound Cognition disorders Discontinued PO USA National Institutes of Health (USA) Originator USA Institution N/A was discovered by the National Institute on Aging QR Pharma Sub-licensee World Biotechnology (NIA) of the US National Institutes of Health Raptor Pharmaceutical Corp Licensee World Pharmaceutical Public (NIH). [CONT.] Research programme: advanced Medifron DBT is developing advanced Advanced glycosylation end-product receptor Alzheimer's disease Preclinical Unknown route South Korea Medifron DBT Originator South Korea Technology provider Public glycosylation end product receptor glycosylation end-product receptor antagonists antagonists antagonists - Medifron for the treatment of Alzheimer's disease. The efficacy of lead candidates have been proven in a 22 transgenic mice model, in preclinical development, underway in South Korea. Advanced glycosylation end-product receptors are established as active transporters of beta amyloid from plasma to the brain. [CONT.] Research programme: advanced Medifron DBT is developing advanced Advanced glycosylation end-product receptor glycosylation end product receptor glycosylation end-product receptor antagonists antagonists antagonists - Medifron for the treatment of Alzheimer's disease. The efficacy of lead candidates have been proven in a 22 transgenic mice model, in preclinical development, underway in South Korea. Advanced glycosylation end-product receptors are established as active transporters of beta amyloid from plasma to the brain. [CONT.] Medifron DBT Owner South Korea Technology provider Public Research programme: allosteric Positive and negative allosteric modulators are A2A PAM Adenosine A2 receptor modulators Alcoholism Preclinical PO Switzerland Addex Pharmaceuticals Originator Switzerland Pharmaceutical Public modulators - Addex Therapeutics being developed by Addex Therapeutics (formerly ADX 68692 Follicle stimulating hormone modulators Alzheimer's disease Preclinical PO Switzerland Addex Therapeutics Owner Switzerland Pharmaceutical Public Addex Pharmaceuticals) for the treatment of a ADX 71441 GABA B receptor agonists Charcot-Marie-Tooth disease Preclinical PO Germany, Netherlands Viva Biotech Collaborator China CRO Private variety of diseases. The compounds are orally ADX 71743 Interleukin 2 receptor modulators Endometriosis Preclinical PO Switzerland available small molecules that have potential use ADX 71943 Interleukin-1 receptor modulators Gastro-oesophageal reflux Preclinical PO Switzerland in overactive bladder, gastro-oesophageal reflux ADX 92639 Metabotropic glutamate receptor 2 modulators Major depressive disorder Preclinical PO Switzerland disease (GERD), endometriosis, pain, urinary incontinence, glaucoma, depression, anxiety, ADX-71743 Metabotropic glutamate receptor 7 modulators Muscle spasticity Preclinical PO Switzerland Alzheimer's disease, type [CONT.] ADX-71943 Metabotropic glutamate receptor modulators Overactive bladder Preclinical PO Switzerland

ADX-92639 Orexin receptor type 2 modulators Pain Preclinical PO Switzerland ADX68692 Ovarian follicle modulators Prostate cancer Preclinical PO Switzerland ADX71441 TrkB receptor agonists Urinary incontinence Preclinical PO Switzerland ADX71743 TrkB receptor modulators [CONT.] Anxiety disorders Research PO Switzerland 23 ADX71943 Gout Research PO Switzerland ADX92639 Huntington's disease Research PO Switzerland Cpd 23 Inflammatory bowel diseases Research PO Switzerland FSHR/LHR NAM for sex hormone dependent Osteoarthritis Research PO Switzerland tumours and reproductive system disorders - Addex Therapeutics GABA-BR PAM for overactive bladder - Addex Parkinson's disease Research PO Switzerland

IL1R1 NAM (CD121a) Post-traumatic stress disorders Research PO Switzerland mGluR2 NAM Psoriasis Research PO Switzerland mGluR7 NAM Rheumatoid arthritis Research PO Switzerland Orexin 2R NAM Sleep disorders Research PO Switzerland TNFR1 NAM (CD120a) Type 2 diabetes mellitus Research PO Switzerland TNFR1 NAM (TNF receptor superfamily) [CONT.] Contraception Discontinued(Preclinical) PO Switzerland

Osteoporosis Discontinued(Preclinical) PO Switzerland Research programme: alpha-7 EnVivo Pharmaceuticals is developing selective, EVP 4473 Alpha7 nicotinic acetylcholine receptor agonists Alzheimer's disease Preclinical PO USA Bayer HealthCare Originator Germany Pharmaceutical Public nicotinic acetylcholine receptor orally active alpha-7 nicotinic acetylcholine agonists - EnVivo Pharmaceuticals receptor (alpha7-nAChR) agonists for the treatment of cognitive decline in patients with Alzheimer's disease (AD) and schizophrenia. The 24 rationale behind selective activation of alpha7- nAChRs is to enhance cognition without causing the adverse events associated with overactivation of other nAChRs or muscarinic EVP-4473 Schizophrenia Preclinical PO USA Bayer HealthCare Pharmaceuticals Owner Germany Pharmaceutical Public acetylcholine receptors [CONT.] EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private Research programme: alpha-7 Roche are developing orally active, nicotinic alpha7 nAChR agonists - Memory Alpha7 nicotinic acetylcholine receptor agonists Alzheimer's disease Preclinical PO USA Memory Pharmaceuticals Originator USA Biopharmaceutical Public nicotinic acetylcholine receptor alpha-7 (alpha7) receptor agonists for the Pharmaceuticals/Roche agonists - Roche treatment of various central nervous system disorders (CNS), particularly Alzheimer's disease 25 (AD) and cognitive impairment associated with schizophrenia (CIAS). The nicotinic alpha7 receptor acts to promote neuronal function, Nicotinic alpha-7 receptor agonists - Memory Nicotinic receptor agonists Schizophrenia Preclinical PO USA Memory Pharmaceuticals Owner USA Biopharmaceutical Public acting on synaptic plasticity and cytoprotection. Pharmaceuticals/Roche [CONT.] Research programme: alpha7 Bionomics is developing positive allosteric BNC 1881 Alpha7 nicotinic acetylcholine receptor Alzheimer's disease Preclinical Unknown route Australia Bionomics Originator Australia Biotechnology Public nicotinic acetylcholine receptor modulators (PAMs) of the alpha7 nicotinic modulators modulator therapeutics - Bionomics acetylcholine receptor (nAChR) for the treatment of Alzheimer's disease and cognitive impairment 26 related to conditions such as attention deficit hyperactivity disorder (ADHD), mood and anxiety BNC 375 Cognition disorders Preclinical Unknown route Australia Bionomics Owner Australia Biotechnology Public disorders, multiple sclerosis, Parkinson's disease, BNC1881 and schizophrenia. [CONT.] BNC375 Research programme: Alzheimer's WisTa Laboratories Ltd., a wholly owned Alzheimer's disease (Diagnosis) Preclinical Unknown route Singapore Bayer HealthCare Pharmaceuticals Owner Germany Pharmaceutical Public and Parkinson's disease diagnostic subsidiary of TauRx Pharmaceuticals, is agents - Bayer HealthCare collaborating with Bayer HealthCare Pharmaceuticals/TauRx Pharmaceuticals (formerly Bayer Schering Pharma) in the development of specific markers 27 that will aid in the diagnosis and management of Tau-protein related Alzheimer's disease (AD), using brain-imaging technology. The programme Parkinson's disease (Diagnosis) Preclinical Unknown route Singapore Bayer Schering Pharma Originator Germany Pharmaceutical Public may also have potential in the development of WisTa Laboratories Originator Singapore Pharmaceutical Private diagnostics for Parkinson's disease [CONT.] WisTa Laboratories Owner Singapore Pharmaceutical Private Research programme: Alzheimer's INVENT Pharmaceuticals is developing small Undefined mechanism Alzheimer's disease Preclinical Unknown route USA INVENT Pharmaceuticals Originator USA Biotechnology Private disease and cognition disorder molecule therapeutics for the treatment of therapeutics - INVENT Alzheimer's disease and age-related cognitive Pharmaceuticals and memory impairment. The company utilises its proprietary site-specific drug design and 28 discovery platform for creation of new candidates. INVENT is actively seeking partners for potential Cognition disorders Preclinical Unknown route USA INVENT Pharmaceuticals Owner USA Biotechnology Private drug discovery, and drug development and commercialisation collaborations.

Memory disorders Preclinical Unknown route USA Research programme: Alzheimer's Avid Radiopharmaceuticals, a molecular imaging Tau tangle diagnostic program Positron-emission tomography enhancers Alzheimer's disease (Diagnosis) Preclinical Unknown route USA Avid Radiopharmaceuticals Originator USA Technology provider Public disease diagnostics - Avid subsidiary of Eli Lilly, is developing positron Radiopharmaceuticals emission tomography (PET) tracers for the diagnosis of Alzheimers disease (AD). AD 29 hallmarks such as cognitive impairment and neuronal circuit degeneration can be correlated with the severity of tau abnormalities and Avid Radiopharmaceuticals Owner USA Technology provider Public neurofibrillary tangles (NFT) burden. [CONT.] Siemens Medical Solutions Originator USA Technology provider Public Research programme: Alzheimer's The Blanchette Rockefeller Neurosciences Alzheimer's disease (Diagnosis) Preclinical Unknown route USA Blanchette Rockefeller Neurosciences Institute Originator USA Institution N/A disease diagnostics and therapeutics - Institute (BRNI) and Neurotrope BioScience are Blanchette Rockefeller collaborating to develop and commercialise 30 Neurosciences Institute/Neurotrope diagnostic and therapeutic agents for Alzheimer's BioScience disease. Development is at the preclinical stage in the US. Alzheimer's disease Preclinical Unknown route USA Neurotrope BioScience Originator USA Biotechnology Research programme: Alzheimer's Lay Line Genomics is researching several Anti-Abeta oligomers - LLG Amyloid beta-protein inhibitors Alzheimer's disease (Diagnosis) Preclinical Unknown route Italy Lay Line Genomics Originator Italy Biopharmaceutical Private disease diagnostics and therapies - products for use as diagnostics and/or therapies Anti-beta-amyloid oligomers - LLG Nerve growth factor stimulants Alzheimer's disease Preclinical Unknown route Italy Lay Line Genomics Owner Italy Biopharmaceutical Private 31 Lay Line Genomics for Alzheimer's disease. Preclinical development Anti-proNerve Growth Factor - LLG is underway in Italy. Anti-proNGF - LLG Diagnostic antibody IM13 - LLG NGF-based therapy - LLG Research programme: Alzheimer's VITRUVIAN BioMedical is developing a DNA Amyloid beta 42 DNA vaccine for Alzheimer's Immunostimulants Alzheimer's disease Preclinical Unknown route USA Nuron Biotech Licensee World Biotechnology Private disease DNA vaccine - VITRUVIAN amyloid beta 42 (Abeta42) vaccine for treatment disease - Nuron Biotech BioMedical/Nuron Biotech of Alzheimer's disease (AD). Unlike a traditional vaccine for AD, this vaccine does not contain Abeta itself, but rather it contains a piece of the 32 gene encoding the Abeta protein. Once in the body, its is expected that the vaccine will stimulate an immune response in which antibodies that bind to and significantly reduce University of Texas Southwestern Medical Center Originator USA University N/A Abeta are produced [CONT.] VITRUVIAN BioMedical Owner USA Biotechnology Research programme: Alzheimer's NasVax in Israel is developing Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Israel NasVax Originator Israel Biopharmaceutical Public disease immunotherapeutics - immunotherapeutic products for Alzheimer's NasVax disease. The company is developing two products based on BBS technology. The two products are 33 a monoclonal antibody (MAb) and a vaccine that is designed to elicit antibodies with similar specificity to the MAb. Development is at the preclinical stage. [CONT.] Research programme: Alzheimer's NasVax in Israel is developing disease immunotherapeutics - immunotherapeutic products for Alzheimer's NasVax disease. The company is developing two products based on BBS technology. The two products are 33 a monoclonal antibody (MAb) and a vaccine that is designed to elicit antibodies with similar specificity to the MAb. Development is at the preclinical stage. [CONT.] Immunostimulants NasVax Owner Israel Biopharmaceutical Public Research programme: Alzheimer's Acumen Pharmaceuticals is developing anti-ADDL antibodies Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Injection USA Acumen Pharmaceuticals Licensee USA Biotechnology disease immunotherapy - immunotherapies against amyloid beta-derived Acumen/Merck diffusible ligand (ADDL). ADDLs are highly ordered aggregates of amyloid beta1-42 34 peptides. The company is developing antibodies and vaccines against ADDLs to delay the progression of Alzheimer's disease, prevent its onset, and potentially restore cognitive function HuC 091 Northwestern University Originator USA University N/A in patients with memory-related disorders. HuC091 Northwestern University Owner USA University N/A Research programme: Alzheimer's Prana[CONT.] Biotechnology is developing an 4,00E+10 Immunostimulants Alzheimer's disease Preclinical Parenteral Australia Prana Biotechnology Originator Australia Biotechnology Public disease immunotherapy - Prana immunotherapy for Alzheimer's disease. The Biotechnology research is assessing the effectiveness of the technology to enhance the production of antibodies as an effective Alzheimer's disease 35 treatment. Prana have developed monoclonal antibodies against a unique form (a conformational epitope) of beta-amyloid which is produced as a result of the oxidative processes central to the toxic pathway in Alzheimer's Prana Biotechnology Owner Australia Biotechnology Public Research programme: Alzheimer's Medeiadisease Therapeutics[CONT.] is developing MDA 208C, a MDA-208C Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Finland Medeia Therapeutics Originator Finland Pharmaceutical Private disease stem cell therapy - Medeia stem cell therapy for the treatment of Therapeutics Alzheimer's disease (AD). The company is using its MDA 200C cell-based therapy platform involving stem cells derived from bone marrow. 36 These cells may be recruited into the central nervous system (CNS) and stimulated using its proprietary technology and pharmacological agents as a disease-modifying approach for the clearance of beta-amyloid (Abeta) peptide deposits/accumulation [CONT.] Cell replacements Medeia Therapeutics Owner Finland Pharmaceutical Private Research programme: Alzheimer's The Institute of Medicinal Molecular Design, Inc. IMD-4690 Plasminogen activator inhibitor-1 inhibitors Alzheimer's disease Preclinical PO Japan Institute of Medicinal Molecular Design Originator Japan Pharmaceutical Private disease therapeutic - Institute of (IMMD) is developing IMD 4690, an orally Medicinal Molecular Design administered inhibitor of PAI-1 (plasminogen 37 activator inhibitor-1), for the treatment of Alzheimer's disease. IMD 4690 is undergoing preclinical development in Japan. Institute of Medicinal Molecular Design Owner Japan Pharmaceutical Private Research programme: Alzheimer's AC Immune has a research programme ACI-518 Alzheimer's disease Preclinical Unknown route Switzerland AC Immune Originator Switzerland Biotechnology Private disease therapeutics - AC Immune investigating therapeutics for the treatment of Alzheimer's disease. The programme is investigating Morphomers™ which are non- 38 covalent complexes of small molecules. The Morphomers™ are designed to specifically bind to misfolded proteins and alter the conformation of the protein to a benign state. [CONT.] ACI-636 AC Immune Owner Switzerland Biotechnology Private Research programme: Alzheimer's AgeneBio is developing small-molecule GABA modulators Alzheimer's disease Preclinical Unknown route USA AgeneBio Originator USA Pharmaceutical Private disease therapeutics - AgeneBio therapeutics for the treatment of amnestic mild cognitive impairment, which is a borderline condition between normal ageing and Alzheimer's disease. Progression to Alzheimer's disease 39 occurs in approximately 15% of patients with amnestic mild cognitive impairment. AgeneBio is designing drug candidates to potentially stabilise neural activity, which has been shown to be excessive in cognitive disorders such as amnestic mild cognitive impairment [CONT.] Mild cognitive impairment Preclinical Unknown route USA AgeneBio Owner USA Pharmaceutical Private Research programme: Alzheimer's Amgen Inc is developing orally available small AMG-0683 BACE1 protein inhibitors Alzheimer's disease Preclinical PO USA Amgen Originator USA Large Pharma, Biotechnology Public disease therapeutics - Amgen molecule BACE (beta-site APP-cleaving enzyme) inhibitors for the treatment of Alzheimer's disease. Preclinical development is ongoing in the US.

40 Cerebral deposition of amyloid beta peptide AMG0683 Amgen Owner USA Large Pharma, Biotechnology Public (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on the proteolytic cleavage of the amyloid precursor protein (APP) by two proteases, beta- secretase and gamma-secretase [CONT.]

CMP 015 Research programme: Alzheimer's Applied NeuroSolutions (formerly Molecular Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Applied NeuroSolutions Originator USA Biopharmaceutical Public disease therapeutics - Applied Geriatrics Corporation), in collaboration with Eli NeuroSolutions/Eli Lilly Lilly, is using in vitro screens in a combinatorial 41 chemistry programme that aims to discover novel therapeutics for the treatment of Alzheimer's disease (AD). Development is at the Applied NeuroSolutions Owner USA Biopharmaceutical Public research stage in the US. [CONT.] Eli Lilly Licensee World Large Pharma, Pharmaceutical Public Research programme: Alzheimer's Archer Pharmaceuticals, a spin-off company of ARC 050 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical Unknown route USA Archer Pharmaceuticals Originator USA Pharmaceutical Private disease therapeutics - Archer The Roskamp Institute, is developing compounds Pharmaceuticals for the treatment of Alzheimer's disease (AD). The Roskamp Institute is devoted to understanding causes and finding cures for 42 neuropsychiatric and neurodegenerative disorders and addictions. Archer Pharmaceuticals aims to find existing drugs that can be repositioned into AD therapies and to use these ARC 069 Calcium channel antagonists Archer Pharmaceuticals Owner USA Pharmaceutical Private drugs as templates for the development of new, ARC050 more effective drugs. [CONT.] ARC069 Research programme: Alzheimer's Asceneuron (a Merck Serono spin-off company) Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Switzerland Merck Serono Originator Switzerland Biopharmaceutical Public disease therapeutics - Asceneuron is developing small-molecule therapeutics for the potential treatment of Alzheimer's disease and other tau protein-related neurological disorders. The research will initially focus on three drug discovery programmes that were in preclinical 43 development with Merck Serono. Compounds identified through these programmes will target Tau protein and amyloid-beta peptides, and are expected to improve cognitive function. Preclinical development is underway in Switzerland. [CONT.] Tau protein inhibitors Merck Serono Owner Switzerland Biopharmaceutical Public Research programme: Alzheimer's Evotech and Boehringer Ingleheim are BACE1 protein inhibitors Alzheimer's disease Preclinical Unknown route Austria, Germany Boehringer Ingelheim Licensee Germany Large Pharma, Pharmaceutical Private disease therapeutics - Boehringer collaboratively investigating potential points of Ingleheim/Evotec AG intervention in the treatment of Alzheimer's disease. Evotec utilises a Fragment Based Drug Discovery (FBDD) and screening platform to 44 identify small molecules in a biologically relevant environment. A library of 20,000 fragments and protein-ligand X-ray crystallography allow Evotech to progress fragment programmes to Evotec AG Originator Germany Pharmaceutical Public identify lead structures and preclinical Evotec AG Owner Germany Pharmaceutical Public development candidates [CONT.] Research Institute of Molecular Pathology Collaborator Austria Institution N/A Research programme: Alzheimer's Senexis is investigating small molecule, peptide- Abeta oligomerisation inhibitors Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Intracerebro ventricular United Kingdom BTG Originator United Kingdom Pharmaceutical Public disease therapeutics - BTG/Senexis based inhibitors of amyloid-beta (Abeta)-induced toxicity as well as neuroinflammation for the Amyloid-beta oligomerisation inhibitors BTG Owner United Kingdom Pharmaceutical Public treatment of Alzheimer's disease (AD) and other amyloid-associated diseases. Toxic oligomers are BGC 200406 Senexis Licensee World Company created by Abeta aggregation, which is 45 considered key to the onset of AD. Senexis has in- licensed three small molecule candidates comprising BGC 201178 [RS 1178], BGC 200406 [RS 0406] and BGC 200466 [RS 0466] from BTG [CONT.] Research programme: Alzheimer's Senexis is investigating small molecule, peptide- Amyloid beta-protein inhibitors disease therapeutics - BTG/Senexis based inhibitors of amyloid-beta (Abeta)-induced toxicity as well as neuroinflammation for the treatment of Alzheimer's disease (AD) and other amyloid-associated diseases. Toxic oligomers are created by Abeta aggregation, which is BGC 200466 45 considered key to the onset of AD. Senexis has in- BGC 201178 licensed three small molecule candidates RS 0406 comprising BGC 201178 [RS 1178], BGC RS 0466 200406 [RS 0406] and BGC 200466 [RS 0466] RS 1178 from BTG [CONT.] SEN 1269 SEN-1269 SEN1269 Research programme: Alzheimer's Hawthorn is developing haw AD14, an orally- haw AD14 Alzheimer's disease Preclinical PO USA CoPlex Therapeutics Originator USA Pharmaceutical Private disease therapeutics - CoPlex administered small molecule originated by CoPlex Therapeutics/Hawthorn Therapeutics, which may have potential in the Pharmaceuticals treatment of Alzheimer's disease. The compound has been shown to significantly decrease levels 46 of amyloid beta (Abeta), as well as tau phosphorylation activity in preclinical studies. These represent key components of the amyloid plaques and paired helical filaments which comprise the neurofibrillary tangles in hawAD14 CoPlex Therapeutics Owner USA Pharmaceutical Private Alzheimer's disease [CONT.] Hawthorn Pharmaceuticals Licensee World Pharmaceutical Private Research programme: Alzheimer's Daewoong Pharmaceutical is developing oral DWJ 501 Undefined mechanism Alzheimer's disease Preclinical PO South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public disease therapeutics - Daewoong therapeutics for the treatment of Alzheimer's Pharmaceutical disease. DWJ 501, a lead candidate from the programme, is a herbal extract. Daewoong is 47 also conducting research to identify new chemical entities that may have efficacy in treating the disease. The programme is in preclinical development in South Korea. [CONT.] DWJ501 Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public Research programme: Alzheimer's ENKAM Pharmaceuticals is developing a peptide FGL-S Fibroblast growth factor receptor modulators Alzheimer's disease Preclinical Parenteral Denmark ENKAM Pharmaceuticals A/S Originator Denmark Biotechnology Private disease therapeutics - ENKAM compound, FGLS, for the treatment of FGLS Cognition disorders Preclinical Parenteral Denmark ENKAM Pharmaceuticals A/S Owner Denmark Biotechnology Private Alzheimer's disease and potentially other Forenap Collaborator France CRO Private conditions that feature impaired cognition, such 48 Lundbeck A/S Collaborator Denmark Large Pharma, Pharmaceutical Public as Parkinson's disease and stroke. FGLS is one of Prague Psychiatric Center Collaborator Czech Republic Institution N/A a family of compounds known as FGL (or FGL Qualissima Collaborator France CRO Private peptides) that function as allosteric fibroblast University Hospital of Cologne Collaborator Germany Hospital N/A growth factor receptor modulators. [CONT.] University of Copenhagen Collaborator Denmark University N/A Research programme: Alzheimer's KaloBios Pharmaceuticals is investigating an Granulocyte macrophage colony stimulating Alzheimer's disease Preclinical Parenteral USA KaloBios Pharmaceuticals Originator USA Biopharmaceutical Private disease therapeutics - KaloBios antibody to granulocyte macrophage colony- factor antagonists Pharmaceuticals stimulating factor (GM-CSF) as a potential therapy for Alzheimer's disease. Preclinical studies are in progress in the US. 49 Analysis of brain tissue from patients with KaloBios Pharmaceuticals Owner USA Biopharmaceutical Private Alzheimer's disease has revealed the presence of inflammation caused by proliferation of microglia and astrocytes. [CONT.]

Research programme: Alzheimer's Kareus Therapeutics is developing compounds for DMAD Amyloidogenic protein inhibitors Alzheimer's disease Preclinical Unknown route Switzerland Kareus Therapeutics Originator Switzerland Pharmaceutical Private disease therapeutics - Kareus the treatment of Alzheimer's disease. The Therapeutics company aims to create therapeutics that intervene in the disease causing mechanism, to 50 slow down or block its progression. Kareus is developing a second generation therapeutic, dimethyl acetylenedicarboxylate (DMAD), utilising the company's Karlect chemistry platform and its Bend biology platform. [CONT.] Kareus Therapeutics Owner Switzerland Pharmaceutical Private Research programme: Alzheimer's Medisyn and the Mount Sinai School of Medicine Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Medisyn Technologies Originator USA Biotechnology disease therapeutics - Medisyn are developing therapeutics for the treatment of Alzheimer's disease. Using Medisyn's Forward 51 Engineering™ technology, eight lead compounds have been discovered with significant in vitro activity, two have also been tested in vivo with promising results. [CONT.] Mount Sinai School of Medicine Originator USA University N/A Research programme: Alzheimer's Merz Pharmaceuticals and Tel Aviv University are Undefined mechanism Alzheimer's disease Preclinical Unknown route Germany, Israel Merz Pharmaceuticals GmbH Originator Germany Pharmaceutical Private disease therapeutics - Merz collaborating in a research programme to Pharmaceuticals/Tel Aviv University develop and commercialise therapeutics for Alzheimer's disease. Both parties will jointly 52 Merz Pharmaceuticals GmbH Owner Germany Pharmaceutical Private evaluate candidate compounds identified using Ramot at Tel Aviv University Technology Transfer Israel Technology Transfer Private the University's proprietary drug discovery Tel Aviv University Collaborator Israel University N/A technology. The programme is being conducted Tel Aviv University Technology Provider Israel University N/A in Germany and Israel. Research programme: Alzheimer's Mithridion is undertaking a research programme Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Mithridion Licensee World Biopharmaceutical disease therapeutics - Mithridion to develop next-generation, disease-modifying compounds for the treatment of Alzheimer's disease (AD). Such small molecule drugs are 53 intended to delay or halt AD progression, particularly the degeneration and death of neurons via inhibition of amyloid-beta (Abeta). University of Wisconsin System Originator USA University N/A This approach is expected to preserve memory, University of Wisconsin System Owner USA University N/A cognitive and other brain functions. [CONT.] Wisconsin Alumni Research Foundation Technology Transfer World Technology Transfer Private Research programme: Alzheimer's Neurim Pharmaceuticals is developing Neu AZ1 Undefined mechanism Alzheimer's disease Preclinical Unknown route Israel Neurim Pharmaceuticals Originator Israel Pharmaceutical Private disease therapeutics - Neurim compounds for the treatment of Alzheimer's 54 Pharmaceuticals disease. The mechanism of action is undisclosed. The company has identified Neu AZ1 as a lead Neu-AZ1 Neurim Pharmaceuticals Owner Israel Pharmaceutical Private candidate, and is in preclinical development, NeuAZ1 presumably in Israel. Research programme: Alzheimer's Neuro-Hitech (formerly Q-RNA) is developing 2 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Neuro-Hitech Originator USA Pharmaceutical Public disease therapeutics - Neuro-Hitech therapeutics for the treatment of Alzheimer's disease (AD) that target as well as inhibit amyloid-beta (Abeta) protein and tau protein oligomer formation. The extraneuronal deposition 55 of Abeta plaques and the intraneuronal 3 Tau protein inhibitors Neuro-Hitech Owner USA Pharmaceutical Public accumulation of hyperphosphorylated tau protein 4-Trihydroxybenzophenone as neurofibrillary tangles are implicated in the 4-Amino 1 pathogenesis of AD. Development is at the 1'-azobenzene-3 preclinical stage in the US. [CONT.] 4'-disulfonic acid sodium salt Research programme: Alzheimer's Pain Therapeutics is developing orally available, PTI 125 Microfilament protein inhibitors Alzheimer's disease Preclinical PO USA Pain Therapeutics Originator USA Biopharmaceutical Public disease therapeutics - Pain small molecule compounds for the treatment of Therapeutics Alzheimer's disease. A lead candidate from this programme, known as PTI 125, is in preclinical development in the US. 56 PTI 125 binds with high affinity to filamin A PTI-125 Pain Therapeutics Owner USA Biopharmaceutical Public (FLNA), a microfilament scaffolding protein which has been shown to play an important role in amyloid-beta42 signalling. [CONT.]

Research programme: Alzheimer's Roche is developing inhibitors of beta-secretase R 641 BACE1 protein inhibitors Alzheimer's disease Preclinical Unknown route Switzerland Roche Originator Switzerland Large Pharma, Pharmaceutical Public disease therapeutics - Roche (BACE-1), for the treatment of Alzheimer's disease (AD). The programme is undergoing preclinical development in Switzerland.

57 The accumulation of amyloid beta-peptide R-641 Roche Owner Switzerland Large Pharma, Pharmaceutical Public (Abeta) is the primary cause for AD pathogenesis. Sequential processing of the amyloid precursor protein (APP) by BACE-1 and gamma-secretase results in the formation of Abeta. [CONT.] Research programme: Alzheimer's Roche and Siena Biotech are collaborating on the Undefined mechanism Alzheimer's disease Preclinical Unknown route Switzerland Roche Originator Switzerland Large Pharma, Pharmaceutical Public disease therapeutics - Roche/Siena development of compounds for the treatment of 58 Biotech neurodegenerative disorders, including Alzheimer's disease. Preclinical development is underway in Italy and Switzerland. Neurodegenerative disorders Preclinical Unknown route Italy Siena Biotech Originator Italy Company Research programme: Alzheimer's Senex Biotechnology is undertaking a drug Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Senex Biotechnology Originator USA Biotechnology Private disease therapeutics - Senex discovery programme to develop compounds for Biotechnology the treatment of major age-related diseases, particularly Alzheimer's disease (AD). The company is developing drugs targeting signalling 59 pathways activated in the process of cell senescence or aging. Studies on functional Amyloid beta-protein precursor inhibitors Senex Biotechnology Owner USA Biotechnology Private genomics have revealed that aging cells BACE1 protein inhibitors overproduce proteins causing AD and other age- Signal transduction pathway inhibitors related diseases [CONT.] Transglutaminase inhibitors Research programme: Alzheimer's Senexis is investigating peptide- and non-peptide- SEN1176 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Senexis Originator United Kingdom Company disease therapeutics - Senexis based inhibitors of amyloid-beta (Abeta)-induced toxicity and neuroinflammation for the treatment of Alzheimer's disease (AD) and other amyloid- associated diseases. Toxic oligomers are created 60 by Abeta aggregation, which is considered key to the onset of AD. Development of peptide-based SEN1500 Macrophage inhibitors Senexis Owner United Kingdom Company inhibitors of amyloid aggregation is at the preclinical stage in the UK. [CONT.] SEN1576 SEN304 SEN606 Research programme: Alzheimer's Socratech LLC is developing therapeutics M007 LRPIV Transcription factor modulators Alzheimer's disease Preclinical Unknown route USA Socratech Originator USA Biotechnology Private disease therapeutics - Socratech LLC targeting the vascular system for the treatment of Alzheimer's disease. The vascular system controls cerebral blood flow, transport of molecules across the blood-brain barrier 61 including removal of critical toxins, and the formation of new blood vessels during aging and neurodegenerative disorders. The vascular system plays a key role in initiating the pathology of brain cells and therefore represents a primary therapeutic target. [CONT.] M007-LRPIV Socratech Owner USA Biotechnology Private Research programme: Alzheimer's Sonexa Therapeutics is undertaking a research Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Sonexa Therapeutics Licensee World Biopharmaceutical Private disease therapeutics - Sonexa programme to develop an undisclosed drug for Therapeutics the treatment of Alzheimer's disease (AD). The company has licensed exclusive rights worldwide 62 (except for Japan and certain Asian countries) to the compound from an undisclosed Japanese pharmaceutical company. Development is at the Unknown Originator USA Company preclinical stage. Unknown Owner USA Company Research programme: Alzheimer's Alzhyme, an Australian biotechnology company, ANA-1 Amyloid beta-protein inhibitors Alzheimer's disease (Diagnosis) Preclinical PO Australia Alzhyme Originator Australia Biopharmaceutical Private disease therapies - Alzhyme is developing orally available, peptide analogues for the treatment of Alzheimer's disease. The company has identified two peptides, ANA-1 and ANA-5, which bind to human beta-amyloid 63 (Abeta), the protein found in the plaques which characterise Alzheimer's disease. In preclinical trials, the peptides were able to prevent beta- amyloid-induced toxicity by neutralising the beta- ANA-5 Superoxide dismutase inhibitors Alzheimer's disease Preclinical PO Australia Alzhyme Owner Australia Biopharmaceutical Private amyloid catalytic production of hydrogen ANSTO Radiopharmaceuticals and Industrials Collaborator Australia Company peroxide [CONT.] CSIRO Collaborator Australia Agency Research programme: Alzheimer's Galapagos (formerly BioFocus) and Senexis beta-sheet breakers Amyloid inhibitors Alzheimer's disease Preclinical PO United Kingdom Galapagos NV Originator Belgium Pharmaceutical Public disease therapies - BioFocus/Senexis Limited in the UK are collaborating in the discovery of small molecule beta sheet (beta- sheet) breakers, and novel inhibitors of amyloid- induced toxicity and neuroinflammation, for the 64 potential treatment of Alzheimer's disease. BioFocus' medicinal chemistry capabilities will be used to accelerate the lead discovery of Senexis' compounds. Senexis Originator United Kingdom Company

Research programme: Alzheimer's Biogen Idec is developing therapies for Gamma secretase modulator - Biogen Idec Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical Unknown route Unknown Biogen Idec Originator USA Large Pharma, Biotechnology Public disease therapies - Biogen Idec Alzheimer's disease (AD). In its Form 10-K (filed 4 February 2011), the company reported that a product candidate had entered preclinical trials: a gamma-secretase modulator (or amyloid 65 precursor protein secretase modulator).

The neurodegeneration observed in AD is thought Biogen Idec Owner USA Large Pharma, Biotechnology Public to be a result of a pathological cascade initiated by formation of insoluble plaques caused by the accumulation of amyloid beta (Abeta) peptides [CONT.] Research programme: Alzheimer's Cellzome Inc., and Johnson & Johnson Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical PO USA Cellzome Originator Germany Pharmaceutical Private disease therapies - Cellzome/Ortho- Pharmaceutical Research & Development in the McNeil Pharmaceutical US are collaborating in a research programme focused on identifying orally administered, amyloid precursor protein secretase (gamma- secretase) modulators and tau protein 66 modulators for the treatment of Alzheimer's disease. Cellzome will provide access to its existing Alzheimer's disease programme technology, including insights into its amyloid precursor protein processing pathway map and Tau protein modulators Johnson & Johnson Pharmaceutical Research & Originator USA Pharmaceutical Public new drug targets [CONT.] Development Research programme: Alzheimer's Mazal Plant Pharmaceuticals, a majority owned LMH-123 Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Mazal Plant Pharmaceuticals Originator USA Company disease therapies - Mazal Plant subsidiary of Adavanced Plant Pharmaceuticals, Pharmaceuticals is developing MAALZ [LMH 123] for the treatment of leukaemia. MAALZ is a plant based 67 composition. Preclinical trials with the compound are ongoing in the US.

MAALZ was originally developed by Advanced MAALZ Mazal Plant Pharmaceuticals Owner USA Company Plant Pharmaceuticals Inc (APPI). [CONT.]

Research programme: Alzheimer's Siena Biotech is developing compounds for the SEN 12333 Alpha7 nicotinic acetylcholine receptor agonists Alzheimer's disease Preclinical Unknown route Italy Siena Biotech Originator Italy Company disease therapies - Siena Biotech treatment of neurodegenerative disorders, particularly Alzheimer's disease. One aspect of the research focus involves investigations of nicotinic acetylcholine receptors of the alpha-7 type (alpha-7 nAChR) as potential therapeutic 68 targets. These receptors are expressed in brain regions associated with cognitive function, SEN 34625 Siena Biotech Owner Italy Company regulate cholinergic neurotransmission and have SEN34625 been shown to be down-regulated in Alzheimer's WAY-317538 disease. Development is at the preclinical stage. WYE 103914 [CONT.] WYE-103914 Research programme: Alzheimer's Satori Pharmaceuticals is developing gamma- Alzheimer's disease therapy research programme Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical Unknown route USA Satori Pharmaceuticals Originator USA Company disease therapy - Satori secretase modulators as a disease modifying - Satori Pharmaceuticals Pharmaceuticals therapy for Alzheimer's disease (AD). AD is characterized by the formation of amyloid beta 69 (Abeta) plaques in brain. There are two main forms of Abeta: Abeta40 and Abeta42. Satori's programme aims to selectively reduce Abeta42, which may overcome the adverse effects associated with reducing total Abeta levels. [CONT.] Research programme: Alzheimer's Satori Pharmaceuticals is developing gamma- Amyloid precursor protein secretase modulators disease therapy - Satori secretase modulators as a disease modifying Pharmaceuticals therapy for Alzheimer's disease (AD). AD is characterized by the formation of amyloid beta 69 (Abeta) plaques in brain. There are two main forms of Abeta: Abeta40 and Abeta42. Satori's SPI 014 Satori Pharmaceuticals Owner USA Company programme aims to selectively reduce Abeta42, SPI 1865 which may overcome the adverse effects SPI-014 associated with reducing total Abeta levels. SPI-1865 [CONT.] Research programme: Alzheimer's Thuris Corporation is investigating compounds Alzheimer's disease therapy research programme Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Thuris Corporation Originator USA Pharmaceutical Private disease therapy - Thuris/D-Pharm for the treatment of Alzheimer's disease. Thuris - Thuris/D-Pharm is using its RapidAgingTM technology to identify 70 and develop potential lead candidates. RapidAgingTM is an assay that creates the hallmarks of Alzheimer's disease, in fewer than 6 days, for using as a preclinical screen for Thuris Corporation Owner USA Pharmaceutical Private potential treatments. Research programme: Alzheimer's Atlas Pharmaceuticals is developing an amyloid EB 101 Immunostimulants Alzheimer's disease (Prevention) Preclinical Parenteral USA Atlas Pharmaceuticals Originator USA Pharmaceutical disease vaccine - Atlas beta vaccine formulated into a liposomal Pharmaceuticals adjuvant for the treatment and prevention of 71 Alzheimer's disease. This vaccine, known as EB 101, utilises a novel amyloid beta1-42 core and acts to evoke a Th2 T-cell reaction. Preclinical development is ongoing in the US. EB101 Alzheimer's disease Preclinical Parenteral USA Atlas Pharmaceuticals Owner USA Pharmaceutical Research programme: Alzheimer's DNAVEC and Eisai have entered into a drug Immunostimulants Alzheimer's disease Preclinical Transmucosal Japan DNAVEC Corporation Originator Japan Technology provider Private disease vaccine - DNAVEC/Eisai discovery research agreement to develop a vaccine treatment for Alzheimer's disease. Using DNAVEC's Sendai virus vector, the two companies plan to develop a gene vaccine able to 72 selectively induce production of antibodies against the beta amyloid protein. Under the terms of the agreement, Eisai has rights to develop, manufacture and sell any compounds identified in the collaboration [CONT.] Eisai Co Ltd Originator Japan Large Pharma, Pharmaceutical Public Research programme: Alzheimer's DNAVEC is co-developing a nasal spray vaccine Alzheimer's disease vaccine intranasal research Immunostimulants Alzheimer's disease Preclinical Intranasal Japan DNAVEC Corporation Originator Japan Technology provider Private disease vaccine intranasal - DNAVEC against Alzheimer's disease with the National programme - DNAVEC Institute for Longevity Sciences of the National Center for Geriatrics and Gerontology in Japan.

73 The vaccine is being developed using Sendai National Institute for Longevity Sciences Originator Japan Institution N/A Virus Vectors (SeV), DNAVEC's vector that develops amyloid-beta. The aim of the SeV- based vaccine is to help reduce senile plaques in the brains of patients with Alzheimer's disease. [CONT.] Research programme: Alzheimer's AC Immune is developing new therapies for the Alzheimer's disease vaccine research programme Immunostimulants Alzheimer's disease Preclinical Parenteral Switzerland AC Immune Originator Switzerland Biotechnology Private disease vaccines - AC Immune treatment of Alzheimer's disease, using - AC Immune vaccination or passive immunisation with antibodies. The company has two programmes investigating immunotherapies targeting two 74 different proteins believed to be involved in Alzheimer's disease. Both therapies use AC Immune's antigen technology (SupraAntigen™) which induces changes in the conformation of misfolded proteins, shifting the equilibrium in favour of benign conformations [CONT.] AC Immune Owner Switzerland Biotechnology Private Research programme: Alzheimer's AFFiRiS and GlaxoSmithKline (GSK) are Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral Austria AFFiRiS Originator Austria Biotechnology Private disease vaccines - collaborating in the development of vaccine AFFiRiS/GlaxoSmithKline candidates for the treatment of Alzheimer's disease. The vaccines will be customised using 75 AFFiRiS' Affitope platform technology (Affitom®) and are designed to induce cross-reactive antibodies against a native antigen, without Immunostimulants AFFiRiS Owner Austria Biotechnology Private producing a systemic immune response. [CONT.] GlaxoSmithKline Licensee World Large Pharma, Pharmaceutical Public Research programme: Alzheimer's Intellect Neurosciences is developing therapeutic RV 01 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral USA Intellect Neurosciences Originator USA Biopharmaceutical Public disease vaccines - Intellect approaches, including vaccines and antibodies, Neurosciences for the treatment and prevention of Alzheimer's disease (AD). The company believes that such approaches will potentially overcome the 76 incidence of autoimmune reactions or other RV 02 Immunostimulants Intellect Neurosciences Owner USA Biopharmaceutical Public serious adverse events, which have hampered RV 03 T lymphocyte stimulants University of California at Irvine Collaborator USA University N/A progress in the field of AD therapy. Development RV01 Tau protein inhibitors is at the preclinical stage in the US. [CONT.] RV02 RV03 Research programme: Alzheimer's MAPP Biopharmaceutical is developing Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Intraperitoneal USA Mapp Biopharmaceutical Originator USA Biopharmaceutical disease vaccines - MAPP monoclonal antibodies against amyloid beta- 77 Biopharmaceutical protein (13-28) for the treatment of cognitive deficits associated with Alzheimer's disease (AD). Development is at preclinical stage in the US. Mapp Biopharmaceutical Owner USA Biopharmaceutical Research programme: Alzheimer's Pfizer and Washington University School of Alzheimer's disease Preclinical Unknown route USA Pfizer Originator USA Large Pharma, Pharmaceutical Public disease, cancer, metabolic disorders Medicine at St. Louis have entered into a and respiratory disease therapeutics - collaboration for the discovery of new indications Pfizer/Washington University for a number of Pfizer's existing compounds that 78 have previously undergone preclinical or clinical testing. The identificiation of new uses for Asthma Preclinical Unknown route USA Pfizer Owner USA Large Pharma, Pharmaceutical Public existing compounds is known as indications Cancer Preclinical Unknown route USA Washington University School of Medicine Collaborator USA University N/A discovery. [CONT.] Diabetes mellitus Preclinical Unknown route USA Research programme: amyloid beta Star Scientific, in collaboration with SRQ Bio Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Star Scientific Originator USA Pharmaceutical Public protein inhibitors - Star Scientific (Roskamp Institute), are developing an amyloid beta protein inhibitor for the treatment of neurological disorders, including Alzheimer's 79 disease. Preclinical investigation has produced positive results finding that the compound also has potential to encourage new neuronal cell growth. Preclinical development is ongoing in the Neurological disorders Preclinical Unknown route USA Star Scientific Owner USA Pharmaceutical Public US. Research programme: amyloid beta- Acumen is developing small molecule ADDL therapeutics Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Acumen Pharmaceuticals Originator USA Biotechnology derived diffusible ligand inhibitors - therapeutics for the treatment of Alzheimer's Acumen disease that target amyloid beta-derived diffusable ligands (ADDLs). ADDLs are highly 80 ordered aggregates of amyloid beta1-42 peptides. Soluble ADDLs trigger malfunctions in nerve cell signaling, causing early and reversible memory dysfunction followed by synaptic loss anti-ADDL therapeutics Acumen Pharmaceuticals Owner USA Biotechnology and nerve cell death. [CONT.] Research programme: amyloid beta- Abbott GmbH is developing amyloid-beta (Abeta) A 887755 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral Germany, USA Abbott GmbH & Co. KG Originator Germany Pharmaceutical Public protein inhibitors - Abbott globulomer-selective monoclonal antibodies for the treatment of Alzheimer's disease. Recent research has implicated the role of the Abeta peptide found in amyloid plaques as a causal factor of the disease. However, new studies 81 showed that memory loss and cognitive function were already impaired in patients with Alzheimer's disease before the plaques started forming, providing evidence of the poor correlation between amyloid plaques and dementia in such patients [CONT.] A-887755 Abbott GmbH & Co. KG Owner Germany Pharmaceutical Public Research programme: amyloid beta- Cognition Therapeutics is developing small CT 0093 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Cognition Therapeutics Originator USA Pharmaceutical Private protein inhibitors - Cognition molecule, amyloid beta-protein inhibitors, as a Therapeutics disease-modifying treatment for Alzheimer's disease. The lead candidates inhibit the activity 82 of the oligomeric form of the amyloid beta- protein that interferes with learning and memory. Memory deficits caused by the oligomeric protein are among the earliest changes seen in Alzheimer's disease. [CONT.] Research programme: amyloid beta- Cognition Therapeutics is developing small Amyloid beta-protein inhibitors protein inhibitors - Cognition molecule, amyloid beta-protein inhibitors, as a Therapeutics disease-modifying treatment for Alzheimer's disease. The lead candidates inhibit the activity 82 of the oligomeric form of the amyloid beta- protein that interferes with learning and memory. Memory deficits caused by the oligomeric protein CT 0109 Cognition Therapeutics Owner USA Pharmaceutical Private are among the earliest changes seen in CT0093 Alzheimer's disease. [CONT.] CT0109 Research programme: amyloid Kinexis Inc., a life science R&D company, is Amyloid oligomer small molecule Alzheimer's disease Preclinical Parenteral USA Kinexis Market Licensee World Company oligomer therapeutics - Kinexis developing a variety of amyloid oligomer therapeutics for the treatment of 83 neurodegenerative diseases. The company Amyloid oligomer vaccine Neurodegenerative disorders Preclinical Parenteral USA University of California at Irvine Originator USA University N/A exclusively licensed the intellectual property and Anti-amyloid oligomer MAb Parkinson's disease Preclinical Parenteral USA University of California at Irvine Owner USA University N/A know-how for this programme from the Anti-amyloid oligomer monoclonal antibody University of California, Irvine. [CONT.] Research programme: amyloid Astex Pharmaceuticals and AstraZeneca are AZ 12066871 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical Unknown route United Kingdom Astex Pharmaceuticals Originator USA Pharmaceutical Public precursor protein secretase collaborating on the development of a series of inhibitors - Astex pyrimidine compounds targeting the amyloid AZ-12066871 AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public Pharmaceuticals/AstraZeneca precursor protein secretase, beta-secretase, a key protein implicated in Alzheimer's disease. AZ12066871 84 Astex Pharmaceuticals, a structure-based drug BACE1 inhibitors - Astex discovery company, is providing an initial series Pharmaceuticals/AstraZeneca Beta-secretase inhibitors - Astex of small-molecule, high affinity, beta-secretase Pharmaceuticals/AstraZeneca inhibitors. [CONT.] Memapsin-2 inhibitors - Astex Pharmaceuticals/AstraZeneca Research programme: amyloid Bristol-Myers Squibb is developing gamma BMS 289948 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public precursor protein secretase secretase (gamma-secretase) inhibitors for the inhibitors - Bristol-Myers Squibb treatment of Alzheimer's disease (AD). Lead compounds from this programme include BMS 289948, BMS 299897 and BMS 433796.

The neurodegeneration observed in AD is thought BMS 299897 Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public 85 to be a result of a pathological cascade initiated by formation of insoluble plaques caused by the accumulation of amyloid beta (Abeta) peptides [CONT.] BMS 433796 BMS-289948 BMS-299897 BMS-433796 Research programme: amyloid EnVivo Pharmaceuticals is developing small- EVP 14936 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical PO USA Amorfix Life Sciences Collaborator Canada Biopharmaceutical Public precursor protein secretase molecule, oral amyloid precursor protein inhibitors - EnVivo secretase (gamma-secretase) inhibitors for the treatment of Alzheimer's disease (AD). The 86 company believes that its compounds are brain- permeable and have disease-modifying potential. Lead compounds identified under the programme EVP 15962 EnVivo Pharmaceuticals Originator USA Biopharmaceutical Private include EVP 14936 which has entered into EVP-14936 EnVivo Pharmaceuticals Owner USA Biopharmaceutical Private preclinical development in the US. [CONT.] EVP-15962 Research programme: amyloid Merck & Co. is developing small molecule beta-secretase-1 inhibitors - Merck & Co Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical PO USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public precursor protein secretase inhibitors of amyloid precursor protein secretase inhibitors - Merck & Co (beta-secretase and gamma-secretase) for the treatment of Alzheimer's disease (AD). Preclinical development of a number of compounds is underway in the US.

beta-secretase is a proteolytic enzyme involved gamma-secretase inhibitors - Merck & Co Schering-Plough Originator USA Large Pharma, Pharmaceutical Public in the cleavage of amyloid precursor protein (APP) to produce toxic beta-amyloid (Abeta) 87 peptides 40 and 42 [CONT.]

BACE programme - Merck & Co SCH 1375975 SCH 697466 SCH 723909 SCH 741216 SCH 745966 SCH 747123 SCH-1375975 SCH-745966 Research programme: amyloid NeuroGenetic Pharmaceuticals is developing NGP 555 Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical PO USA NeuroGenetic Pharmaceuticals Owner USA Pharmaceutical precursor protein secretase small molecule modulators of human amyloid modulators - NeuroGenetic precursor protein secretase (gamma-secretase) Pharmaceuticals for the treatment of Alzheimer's disease (AD). The company has identified a series of orally 88 available 2-aminothiazole derivatives that lowered pathogenic beta-amyloid (Abeta) NGP-555 TorreyPines Therapeutics Inc Originator USA Biopharmaceutical Public Abeta42 levels and shifted the cleavage towards NGP555 shorter Abeta peptides (such as Abeta37 , NGX 555 Abeta38) [CONT.] NGX555 Research programme: anti-beta Takeda is developing passive immunotherapy for anti-Abeta antibodies - Takeda Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Injection Japan Takeda Originator Japan Large Pharma, Pharmaceutical Public amyloid antibodies - Takeda the treatment of Alzheimer's disease. Previous work showed vaccination was an effective treatment for Alzheimer's disease but the risk of adverse events associated with the therapy, 89 including meningoencephalitis, prompted Takeda to develop antibodies against beta amyloid BA 27 Takeda Owner Japan Large Pharma, Pharmaceutical Public (Abeta) as a potentially safer option. BA27 Development is at the preclinical stage in Japan. BC 05 [CONT.] BC05 Research programme: anti-beta- Centocor and Johnson & Johnson Pharmaceutical JRF/hAb11/1 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral USA Centocor Originator USA Biopharmaceutical Public amyloid antibodies - Centocor/ Research and Development are developing Johnson & Johnson monoclonal antibodies specific to a truncated form of beta-amyloid (Abeta), for the treatment of Alzheimer's disease. The truncated form of 90 Abeta, Abeta11-40/42, results from further cleavage of the Abeta by the BACE1 enzyme at position 11, and is increased in biological samples from Alzheimer's patients with the Johnson & Johnson Pharmaceutical Research & Originator USA Pharmaceutical Public Swedish mutation in APP [CONT.] Development Research programme: anxiety and AstraZeneca is developing compounds for the 5-HT1A receptor antagonists - AstraZeneca Opioid delta receptor agonists Alzheimer's disease Preclinical Unknown route Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public neurological disorder therapeutics - treatment of anxiety and neurological disorders, AstraZeneca including affective disorders and Alzheimer's disease. Preclinical development is ongoing in the UK, US and Sweden.

AstraZeneca and Columbis University Medical AZ 12320927 Serotonin 1A receptor antagonists Anxiety disorders Preclinical Unknown route United Kingdom AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public 91 Center are also collaborating to examine neurogenesis as a potential pathway for treament of depression and anxiety. [CONT.]

AZ12320927 Serotonin 1B receptor antagonists Major depressive disorder Preclinical Unknown route USA Columbia University Collaborator USA University N/A Karolinska Institute Collaborator Sweden University N/A University of Texas Southwestern Medical Center Collaborator USA University N/A Research programme: apolipoprotein Eli Lilly is developing lentiviral vectors expressing ApoE2 gene therapy - Eli Lilly Apolipoprotein E agonists Alzheimer's disease Preclinical Unknown route USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public E gene therapy - Eli Lilly apolipoprotein E (apoE) isoforms for treatment of Alzheimer's disease (AD). Development is at the preclinical stage in the US.

92 Studies have indicated that direct gene delivery Eli Lilly Owner USA Large Pharma, Pharmaceutical Public of apoE2 via intracerebral administration may prevent or reduce brain amyloid-beta (Abeta) burden and the subsequent development of neuritic plaques. [CONT.] Research programme: apolipoprotein Merck & Co., Inc. is collaborating with the J. Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Merck & Co Market Licensee World Large Pharma, Pharmaceutical Public E therapies - Gladstone David Gladstone Institutes in the development of Institutes/Merck a treatment for neurodegenerative diseases linked to apolipoprotein E (apoE)-regulated 93 pathways, such as Alzheimer's disease (AD). Three forms of apoE, (aopE2, E3 and E4), are involved in the regulation of lipid homeostasis and the maintenance of neuronal integrity and The J. David Gladstone Institutes Originator USA Institution N/A function. [CONT.] The J. David Gladstone Institutes Owner USA Institution N/A Research programme: apolipoprotein Cognosci Inc. of Research Triangle Park (North COG 112 Apolipoprotein E agonists Alzheimer's disease Preclinical Unknown route USA Cognosci Owner USA Pharmaceutical Private E-mimetic peptide therapeutics - Carolina, US) is developing small molecule COG 133 Brain injuries Preclinical Unknown route USA Duke University Originator USA University N/A Cognosci Inc. apolipoprotein E (apoE)-mimetic peptides of ten COG 1410 Multiple sclerosis Preclinical Unknown route USA to seventeen amino acids for the treatment of COG 241 Subarachnoid haemorrhage Preclinical Unknown route USA multiple sclerosis (MS), traumatic brain injury, COG 68 Inflammatory bowel diseases Discontinued(Preclinical) Unknown route USA 94 subarachnoid haemorrhage and Alzheimer's COG112 Chronic lymphocytic leukaemia No development reported(Preclinical) Unknown route USA disease. These compounds may also have potential in the treatment of rheumatoid arthritis COG133 Rheumatoid arthritis No development reported(Preclinical) Unknown route USA and Parkinson's disease. [CONT.] COG1410 Parkinson's disease No development reported(Research) Unknown route USA COG241 COG68 Research programme: apolipoprotein Madera Biosciences is developing small molecule Apolipoprotein E modulators Alzheimer's disease Preclinical Unknown route USA Madera BioSciences Originator USA Biotechnology Private E-targeted Alzheimer's disease compounds that increase the expression of therapeutics - Madera Biosciences apolipoprotein E (apoE) for the treatment of Alzheimer's disease (AD) in the US. Through the 95 increase expression of ApoE, the molecules mediate beta-amyloid clearance from the brain, preventing its accumulation into the plaques that are characteristic of AD. [CONT.] Madera BioSciences Owner USA Biotechnology Private Research programme: BACE1 protein CoMentis (formerly Zapaq) and Astellas Pharma BACE inhibitors - CoMentis BACE1 protein inhibitors Alzheimer's disease Preclinical PO USA Astellas Pharma Licensee World Large Pharma, Pharmaceutical Public inhibitors - Astellas are co-developing orally available, small Pharma/CoMentis molecule inhibitors of BACE1 (beta-amyloid converting enzyme 1 or memapsin 2) as disease- 96 modifying agents for Alzheimer's disease (AD). Disease modifying Alzheimer's disease therapy - CoMentis Originator USA Biopharmaceutical Private beta-secretase is a human brain aspartic CoMentis protease that catalyses the rate-limiting step in OM 991 CoMentis Owner USA Biopharmaceutical Private amyloid-beta (Abeta) peptide production, a key OM 992 Oklahoma Medical Research Foundation Technology Provider USA Institution N/A event in the progression of AD. [CONT.] University of Illinois at Chicago Technology Provider USA University N/A Research programme: BACE1 protein Bristol-Myers Squibb is developing BACE1 (beta- BMS 782450 BACE1 protein inhibitors Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public inhibitors - Bristol-Myers Squibb secretase) inhibitors for the treatment of Alzheimer's disease. BACE is a human brain protease that catalyzes the first step of the two- 97 step amyloid precursor protein (APP) cleavage process, which in turn leads to the formation of toxic beta-amyloid (Abeta)40/42 peptides. Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public [CONT.] Research programme: BACE1 protein Johnson & Johnson Pharmaceutical R&D is BACE1 protein inhibitors Alzheimer's disease Preclinical Unknown route USA Johnson & Johnson Pharmaceutical Research & Originator USA Pharmaceutical Public inhibitors - Johnson & Johnson developing a series of BACE1 (beta-amyloid site Development cleaving enzyme) inhibitors for the treatment of Alzheimer's disease (AD). The amyloid hypothesis is one of the mechanisms through which the etiology of AD may be explained; beta- 98 secretase (BACE) and gamma-secretase cleave amyloid precursor protein (APP) at the N- and C- terminus, respectively, producing the beta- amyloid peptides, Abeta1-40 and Abeta1-42, which subsequently aggregate into neurotoxic Johnson & Johnson Pharmaceutical Research & Owner USA Pharmaceutical Public oligomers and fibrils [CONT.] Development Research programme: BACE1 protein Merck & Co. in the US is developing brain- SCH 1359113 BACE1 protein inhibitors Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public inhibitors - Merck and Co penetrating small-molecule inhibitors of human BACE1 (beta-amyloid converting enzyme, or beta- secretase) as potential treatments for Alzheimer's disease. Several series' of compounds are being investigated and preclinical development is ongoing in the US. 99 It is believed that the amyloid cascade plays a SCH 1682496 Sunesis Pharmaceuticals Originator USA Biopharmaceutical Public significant role in the cause of Alzheimer's disease. [CONT.] SCH 785532 SCH-1359113 SCH-1682496 SCH-785532 Research programme: BACE1 protein Novartis is developing cyclic sulfoxide BACE1 protein inhibitors Alzheimer's disease Preclinical IV Switzerland Novartis Originator Switzerland Large Pharma, Pharmaceutical Public inhibitors - Novartis hydroxyethylamine-based BACE-1 inhibitors for the treatment of Alzheimer's disease. BACE-1 is an aspartyl protease which cleaves amyloid precursor protein to form that N-terminus of 100 Abeta, the major constituent of amyloid plaques. To identify compounds, Novartis has developed a design approach involving X-rays of co- crystallisation of macrocyclic ethanolamine inhibitors with BACE-1 [CONT.] Novartis Owner Switzerland Large Pharma, Pharmaceutical Public Research programme: BACE1 protein Pfizer is developing orally active, small molecule WAC-547415 BACE1 protein inhibitors Alzheimer's disease Preclinical PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public inhibitors - Pfizer inhibitors of beta-secretase (BACE1) for the treatment of Alzheimer's disease. beta-secretase is a human brain protease that catalyzes the first 101 step of the two-step amyloid precursor protein (APP) cleavage process, which in turn leads to the formation of toxic beta-amyloid (Abeta)40/42 peptides. Preclinical development WAY-258131 Wyeth Originator USA Large Pharma, Pharmaceutical Public is underway in the US. [CONT.] WY-24454 Research programme: BACE1 protein Vitae Pharmaceuticals, and Boehringer BACE1 inhibitors - Vitae BACE1 protein inhibitors Alzheimer's disease Preclinical PO USA Boehringer Ingelheim Licensee World Large Pharma, Pharmaceutical Private inhibitors - Vitae Pharmaceuticals Ingelheim, are developing oral BACE1 (bate site APP cleaving enzyme 1) protein inhibitors for the treatment of Alzheimer's disease (AD). The 102 inhibitors have demonstrated the ability to cross the blood-brain barrier and to lower brain amyloid beta (Abeta) peptide following a single Beta secretase inhibitors - Vitae Vitae Pharmaceuticals Originator USA Pharmaceutical Private oral dose in preclinical, in vivo models of AD. Vitae Pharmaceuticals Owner USA Pharmaceutical Private [CONT.] Research programme: beta amyloid Pfizer and Astellas Pharma are developing PD 0118057 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Japan, USA Astellas Pharma Originator Japan Large Pharma, Pharmaceutical Public aggregation inhibitors - Astellas amyloid beta peptide (Abeta) aggregation Pharma/Pfizer inhibitors for the treatment of Alzheimer's disease. Formation of insoluble plaques caused by aggregation of Abeta is thought to initiate a 103 pathological cascade that results in Alzheimer's- related neurodegeneration. Inhibition of protein aggregation with small molecule inhibitors may be a potential way to slow or stop disease progression [CONT.] PD 0202091 Pfizer Originator USA Large Pharma, Pharmaceutical Public Research programme: beta secretase Researchers at Actelion Pharmaceuticals are Research programme: beta-secretase inhibitor Amyloid beta-protein precursor inhibitors Alzheimer's disease Preclinical Unknown route Switzerland Actelion Pharmaceuticals Originator Switzerland Large Pharma, Biopharmaceutical Public inhibitors - Actelion investigating aspartyl protease inhibitors of beta secretase (BACE, BACE1, beta amyloid precursor 104 protein-cleaving enzyme) as potential treatments for Alzheimer's disease. BACE is an enzyme that mediates the deposition of amyloid plaque in the brain. Research programme: beta secretase Researchers at Actelion Pharmaceuticals are Research programme: beta-secretase inhibitor Amyloid beta-protein precursor inhibitors inhibitors - Actelion investigating aspartyl protease inhibitors of beta secretase (BACE, BACE1, beta amyloid precursor 104 protein-cleaving enzyme) as potential treatments for Alzheimer's disease. BACE is an enzyme that mediates the deposition of amyloid plaque in the Actelion Pharmaceuticals Owner Switzerland Large Pharma, Biopharmaceutical Public brain.

Research programme: beta-amyloid Prana Biotechnology is developing a compound Abeta inhibitors - Prana Biotechnology Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO Australia Prana Biotechnology Originator Australia Biotechnology Public inhibitors - Prana Biotechnology library comprising a next-generation class of orally available, platinum-based complexes ('metallocomplexes') with 1,10-phenanthroline- 105 derived ligands as beta-amyloid (Abeta) inhibitors for the treatment of neurodegenerative Metallocomplex programme - Prana Chelating agents Alzheimer's disease (Diagnosis) Research PO Australia Prana Biotechnology Owner Australia Biotechnology Public disorders, particularly Alzheimer's disease (AD). Biotechnology Such compounds bind and block the actual metal- VK-11 Diagnostic imaging enhancers binding site on Abeta peptide in the brain VK-12 Research programme: beta-amyloid Affibody[CONT.] AB is developing Affibody® molecules as Abeta ligands - Affibody Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Sweden Affibody Originator Sweden Biotechnology Private ligands - Affibody small protein ligands that target beta-amyloid (Abeta) for the treatment of Alzheimer's disease (AD). Such ligands stabilise the Abeta peptide 106 and inhibits the formation of toxic Abeta fibrils and plaques in the brain. Development of lead candidates is at the preclinical stage in Sweden. Affibody® molecules Affibody Owner Sweden Biotechnology Private [CONT.] Beta-amyloid ligands - Affibody Research programme: beta-amyloid Chiesi in Italy is developing flurbiprofen beta-amyloid secretion inhibitors Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Italy Chiesi Originator Italy Pharmaceutical Private secretion inhibitors - Chiesi analogues for the potential treatment of patients with Alzheimer's disease. The chronic use of a subset of non-steroidal anti-inflammatory drugs CHF 4801 Chiesi Owner Italy Pharmaceutical Private (flurbiprofen, ibuprofen and indomethacin) has CHF 5022 107 been reported to selectively inhibit the production CHF-5077 of beta amyloid1-42 (Abeta42) in vitro and limit CHF4801 the progression of Abeta plaque pathology in CHF5022 mice over expressing human amyloid precursor CHF5077 protein [CONT.] CHF5096 CHF5105 Research programme: beta-secretase Janssen Pharmaceuticals and Shionogi are Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical PO Japan, USA Janssen Pharmaceuticals Licensee USA Pharmaceutical Public inhibitors - Janssen/Shionogi collaborating to discover, develop and commercialise small molecule oral beta- 108 secretase (BACE) (amyloid precursor protein secretase) inhibitors for the treatment of Alzheimer's disease. Development is at the Shionogi Originator Japan Large Pharma, Pharmaceutical Public preclinical stage in Japan and the US. [CONT.] Shionogi Owner Japan Large Pharma, Pharmaceutical Public Research programme: calpain AbbVie (formerly Abbott Laboratories) is A 705253 Calpain inhibitors Alzheimer's disease Preclinical Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public inhibitors - AbbVie developing calpain inhibitors for potential use in the treatment of Alzheimer's disease (AD). The over activation of calpain, a calcium-dependent 109 cysteine protease, is believed to play a role in the pathophysiology of several neurodegenerative disorders, including AD. [CONT.] A-705253 AbbVie Owner USA Biopharmaceutical Public Research programme: cannabinoid The US biopharmaceutical company Aphios APH 0802 Cannabinoid receptor agonists Alzheimer's disease Preclinical PO USA Aphios Corporation Originator USA Biopharmaceutical Private therapeutics - Aphios Corporation Corporation is developing natural cannabinoid APH-0802 Cachexia Preclinical PO USA Aphios Corporation Owner USA Biopharmaceutical Private products, including lead candidate APH 0802, Cannabinoid therapeutics research programme - Cancer pain Preclinical PO USA derived from the marijuana plant Cannabis Aphios Corporation 110 sativa, for the treatment of a marijuana Delta-9-tetrahydrocannabinol Drug abuse Preclinical PO USA addiction, cancer pain, cachexia in AIDS patients, Delta-9-tetrahydrocannabinolic acid Nausea and vomiting Preclinical PO USA nausea and vomiting, and relief to Alzheimer's Delta-9-THC patients while increasing their appetite. [CONT.] Delta-9-THC nanotech formulation Delta-9-THCA Research programme: cell movement Pharmaxon is developing compounds that Cell mobility activators - Pharmaxon Cell movement activators Spinal cord injuries Preclinical Unknown route France CNRS Originator France Institution N/A activators - Pharmaxon specifically stimulate neural cell mobility and neuroplasticity for the treatment of spinal cord injuries as well as mild cognitive impairment and 111 Alzheimer's disease. A lead candidate generated Polysialyl neural cell adhesion molecule Polysialyl neural cell-adhesion-molecule-agonists Alzheimer's disease Research Unknown route France Pharmaxon Licensee World Biopharmaceutical Private from this research is a polysialyl neural cell mimotope adhesion molecule (PSA-NCAM) mimotope (a PR-21C Mild cognitive impairment Research Unknown route France Schafer-N Originator Denmark Biotechnology Private cyclic 12-amino acid peptide that can PR-21S Universite de la Mediterranee Originator France University N/A conformationally mimic antigenic specificity) PSA-NCAM mimotope University Medical Center Hamburg-Eppendorf Originator Germany University N/A Research programme: central ArmaGen[CONT.] is developing therapies for the AGT 110 Acetylcholinesterase inhibitors Alzheimer's disease (Diagnosis) Preclinical IV USA ArmaGen Technologies Originator USA Biotechnology Private nervous system therapeutics - treatment of central nervous system (CNS) AGT 115 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical IV USA ArmaGen Technologies Owner USA Biotechnology Private ArmaGen disorders utilising their trojan horse delivery AGT 120 Erythropoietin receptor modulators Parkinson's disease Preclinical IV USA system. This delivery system involves binding a AGT 160 Glial cell line-derived neurotrophic factor Poisoning Preclinical Unknown route USA substrate capable of crossing the blood brain modulators barrier (BBB) to a therapeutic agent. [CONT.] AGT 185 Tumour necrosis factor alpha inhibitors Stroke Preclinical IV USA AGT 190 Tumour necrosis factor decoy receptor Brain cancer No development reported(Preclinical) IV USA modulators AGT 3 Tumour necrosis factor inhibitors Brain disorders No development reported(Preclinical) IV USA

112 AGT 3100 Major depressive disorder No development reported(Preclinical) IV USA

AGT-110 Spinal cord injuries No development reported(Preclinical) IV USA

AGT-115 AGT-120 AGT-160 AGT-185 AGT-190 AGT-3 AGT-3100 Research programme: chelating PALUMED SA, in France, is researching copper PA 1637 Chelating agents Alzheimer's disease Preclinical Unknown route France PALUMED Originator France Biotechnology Private agents - PALUMED chelating agents for the treatment of Alzheimer's 113 disease (AD) including lead candidate PA 1637. Preclinical development of PA 1637 is ongoing and PALUMED is preparing it to enter clinical PA1637 PALUMED Owner France Biotechnology Private trials. [CONT.] Research programme: CNS disorder sigma-tau has a research programme directed at ST 1859 Undefined mechanism Alzheimer's disease Preclinical Unknown route Italy sigma-tau SpA Originator Italy Pharmaceutical Private therapies - sigma-tau disorders of the central nervous system (CNS) and peripheral nervous system (PNS). Lead compounds from this programme include ST 114 2472 and ST 1859 for the treatment of schizophrenia and Alzheimer's disease, ST 1936 Depressive disorders Preclinical Unknown route Italy sigma-tau SpA Owner Italy Pharmaceutical Private respectively. Another lead candidate, ST 1936, is ST 2472 Schizophrenia Preclinical Unknown route Italy also in development as a treatment for unipolar ST1936 depressive disorders. [CONT.] ST2472 Research programme: CNS disorders Anavex Life Sciences is developing compounds ANAVEX 1 41 Calcium channel antagonists Alzheimer's disease Preclinical IV Europe Anavex Life Sciences Originator Switzerland Biopharmaceutical Public therapeutics - Anavex Life Sciences targeted at sigma receptors for the treatment of ANAVEX 1-41 Chloride channel modulators Alzheimer's disease Preclinical PO Europe Anavex Life Sciences Owner Switzerland Biopharmaceutical Public the central nervous system (CNS) disorders ANAVEX 19-144 Muscarinic M1 receptor agonists Epilepsy Preclinical Unknown route Europe Alzheimer's disease, epilepsy, depression and Muscarinic M2 receptor antagonists Major depressive disorder Preclinical Unknown route Europe stroke. Pharmacological research has indicated 115 Muscarinic M3 receptor antagonists Stroke Preclinical Unknown route Germany that sigma-1 and sigma-2 receptors act as NMDA receptor antagonists intracellular amplifiers, creating a supersensitive Serotonin modulators state of signal transduction in biochemical Sigma-1 receptor agonists pathways, which might contribute to these Sodium channel antagonists disorders [CONT.] Sodium channel modulators Research programme: CNS disorders Intra-Cellular Therapies is developing orally- ITI-009 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO USA Intra-Cellular Therapies Originator USA Company therapeutics - Intra-Cellular available, small molecule therapeutics for the Therapies treatment of various central nervous system (CNS) disorders, including Alzheimer's disease 116 (AD). The company is using its CNSProfile™ technology platform to select and optimise its Dopamine D1 receptor agonists Intra-Cellular Therapies Owner USA Company internally-derived and proprietary drug Dopamine receptor agonists Takeda Licensee World Large Pharma, Pharmaceutical Public candidates as well as to evaluate potential in- licensed candidates. [CONT.] Research programme: CNS disorders Intra-Cellular Therapies is developing orally- ITI-009 therapeutics - Intra-Cellular available, small molecule therapeutics for the Therapies treatment of various central nervous system (CNS) disorders, including Alzheimer's disease 116 (AD). The company is using its CNSProfile™ technology platform to select and optimise its internally-derived and proprietary drug candidates as well as to evaluate potential in- Type 1 cyclic nucleotide phosphodiesterase licensed candidates. [CONT.] inhibitors Research programme: CNS disorders Mapreg SAS of France is developing a series of 3-Methoxy-pregnenolone Microtubule-associated protein stimulants Alzheimer's disease Preclinical Parenteral France Mapreg Originator France Biotechnology Private therapeutics - Mapreg synthetic neurosteroids derived from pregnenolone for the treatment of various central nervous system (CNS) disorders, including spinal cord injuries, traumatic brain injuries and stroke along with depressive disorders, schizophrenia 117 and Alzheimers's disease. These pregnenolone derivatives do not exhibit metabolic interactions Pregnenolone analogues Tubulin polymerisation promoters Brain injuries Preclinical Parenteral France Mapreg Owner France Biotechnology Private with other steroid hormones and are designed for Pregnenolone derivatives Depressive disorders Preclinical Parenteral France administration by injection with the ability to Schizophrenia Preclinical Parenteral France cross the blood-brain barrier. Development is at Spinal cord injuries Preclinical Parenteral France the preclinical stage in France. [CONT.] Stroke Preclinical Parenteral France Research programme: CNS disorders MedGenesis Therapeutix Inc is developing Undefined mechanism Alzheimer's disease Preclinical Unknown route Canada MedGenesis Therapeutix Originator Canada Biopharmaceutical Private therapeutics - MedGenesis compounds to treat diseases of the central Therapeutix nervous system (CNS) including Alzheimer's disease, Parkinson's disease and brain cancers. 118 The company is using its Convection Enhanced Delivery (CED) methods to target and transport therapeutic agents to the relevant area in the Glioblastoma Preclinical Unknown route Canada MedGenesis Therapeutix Owner Canada Biopharmaceutical Private CNS. [CONT.] Parkinson's disease Preclinical Unknown route Canada Research programme: cognitive Cenomed BioSciences, in collaboration with the CB 2433 Cholinergic receptor modulators Alzheimer's disease Preclinical Unknown route USA Cenomed BioSciences Licensee World Biopharmaceutical Private disorders therapeutics - Cenomed Medical College of Georgia Research Institute, is CB-2 Mild cognitive impairment Preclinical Unknown route USA Medical College of Georgia Originator USA Institution N/A BioSciences developing small molecules that target 433 Medical College of Georgia Owner USA Institution N/A components of acetylcholine neurons and thereby CB-2433 enhance cholinergic function. These agents are CB2433 119 being developed to treat cognitive disorders such CM 2433 as mild cognitive impairment and Alzheimer's CM 2450 disease, while avoiding cholerinergic side effects. CM-2 [CONT.] 433 CM-2 450 Research programme: colostrinin ReGen Therapeutics Plc is characterising of the Colostinin™ Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO United Kingdom Nonindustrial source Originator Unknown Institution N/A constituent peptides - ReGen biologically active peptide constituents of Therapeutics Colostinin™ in order to identify properties that might lend them towards development as pharmaceutical agents for CNS 120 neurodegenerative diseases and cancer. The company hopes to identify smaller molecular Antioxidants Cancer Research Unknown route United Kingdom Nonindustrial source Owner Unknown Institution N/A weight therapeutics that have similar or greater Apoptosis inhibitors ReGen Therapeutics Market Licensee United Kingdom Company activity than Colostrinin™. [CONT.] Cell differentiation stimulants Research programme: cytokine Transition Therapeutics is developing small Minozac Cytokine inhibitors Alzheimer's disease Preclinical PO Canada, USA Chinese Academy of Sciences Collaborator China Institution N/A inhibitors - Transition Therapeutics molecule cytokine inhibitors for the potential treatment of neurological and inflammatory disorders. A lead candidate, TT 302, is in preclinical development in the US and Canada for 121 the potential treatment of Alzheimer's disease MW 015188WH Rheumatoid arthritis Preclinical PO Canada, USA InnovatePharma Collaborator USA Pharmaceutical Private and rheumatoid arthritis. Development for the MW01-5-188WH Alzheimer's disease Discontinued(Preclinical) PO China Northwestern University Originator USA University N/A latter indication is being conducted in conjunction TT302 Brain injuries Discontinued(Preclinical) PO Canada, China Northwestern University Owner USA University N/A with the University of California at Los Angeles Multiple sclerosis Discontinued(Preclinical) PO Canada, China, USA Transition Therapeutics Licensee World Biopharmaceutical Public (California, USA) [CONT.] Parkinson's disease Discontinued(Preclinical) PO Canada, USA University of California at Los Angeles Collaborator USA University N/A Research programme: dimebolin ChemDiv is undertaking a research programme Cholinesterase inhibitors Alzheimer's disease Preclinical Unknown route USA ChemDiv Originator USA CRO Private analogues - ChemDiv to develop a series of small molecule, water- soluble, dimebolin analogues for the treatment of cognition disorders and Alzheimer's disease (AD). This series of dimebolin analogues has 122 been found to penetrate the blood-brain barrier and possess promising cognition-enhancing properties. Optimised lead compounds are G protein-coupled receptor modulators Cognition disorders Preclinical Unknown route USA ChemDiv Owner USA CRO Private undergoing preclinical testing in the US. [CONT.] NMDA receptor antagonists Serotonin 6 receptor antagonists Research programme: DKK1 Siena Biotech is developing small molecule Wnt protein modulators Alzheimer's disease Preclinical Unknown route Italy Siena Biotech Originator Italy Company antagonists - Siena Biotech selective antagonists of the Dickkopf-1 (DKK1) protein as a treatment for Alzheimers disease (AD). It has been demonstrated that DKK1 123 causes the inhibition of the Wnt signalling pathway, which when impaired causes an increase in the expression of amyliod-beta peptide in neuronal cultures and in patients Siena Biotech Owner Italy Company suffering from AD. [CONT.] Research programme: DYRK Diaxonhit is developing small molecule, selective DYRK kinase inhibitors Alzheimer's disease Preclinical Unknown route USA Diaxonhit Originator France Pharmaceutical inhibitors - Diaxonhit DYRK1a/1b (dual specificity tyrosine- phosphorylation-regulated kinase) inhibitors for the treatment of Alzheimer's disease and Down syndrome. DYRK1a/1b kinases are involved in several pathways associated with CNS disorders 124 or cell proliferation. Diaxonhit believes that DYRK1a kinase inhibitors have the potential to be disease modifying agents for tauopathies and Tau-mediated amyloid beta toxicity, including Alzheimer's disease and Down syndrome [CONT.] Down syndrome Preclinical Unknown route USA Diaxonhit Owner France Pharmaceutical Research programme: endopeptidase American Life Science Pharmaceuticals is acetyl-L-leucyl-L-valyl-L-lysinal-aldehyde Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical Unknown route USA American Life Science Pharmaceuticals Originator USA Pharmaceutical inhibitors - American Life Science developing small molecule inhibitors of Pharmaceuticals proprietary endopeptidase targets for the treatment of Alzheimer's disease. The company is focusing on the development of secretase and 125 cathepsin B endopeptidase targets. Secretases cleave amyloid precursor protein (APP) into beta- CA 074Me Cathepsin B inhibitors American Life Science Pharmaceuticals Owner USA Pharmaceutical amyloid (Abeta) peptides which are thought to be CA074Me Endopeptidase inhibitors responsible for the pathology of Alzheimer's E 64d disease [CONT.] E64d Research programme: endothelin Chicago Labs is developing endothelin (ET) Endothelin receptor antagonists Alzheimer's disease Preclinical Unknown route USA Chicago Labs Originator USA Company receptor antagonists - Chicago Labs receptor antagonists for the treatment of pain, stroke, and Alzheimer's disease. Endothelin 126 receptors are prevalent throughout the vasculature and are responsible for vasodilation and vasoconstriction. Development is at the Pain Preclinical Unknown route USA Chicago Labs Owner USA Company preclinical stage in the US. Stroke Preclinical Unknown route USA Research programme: G protein- Euroscreen in Belgium has a broad research ESN-282 G protein-coupled receptor modulators Alzheimer's disease Preclinical Unknown route Belgium Euroscreen Originator Belgium Company coupled receptor modulators - programme focussed on discovering small Euroscreen molecule therapeutics that target G protein- coupled receptors (GPCRs). Lead compounds under investigation include ESN 282, a GPR43 ESN-401 G-protein coupled receptor 43 modulators Amyotrophic lateral sclerosis Preclinical Unknown route Belgium Euroscreen Owner Belgium Company 127 modulator in development for ulcerative collitis, ESN-502 Brain injuries Preclinical Unknown route Belgium and ESN 502, a GPR modulator investigated for ESN-603 Parkinson's disease Preclinical Unknown route Belgium neurodegenerative diseases such as Alzheimer's, Ulcerative colitis Preclinical Unknown route Belgium Parkinson's, amyotropic lateral sclerosis (ALS) Obesity Research Unknown route Belgium and traumatic brain injury [CONT.] Type 2 diabetes mellitus Research Unknown route Belgium Inflammation No development reported(Research) Unknown route Belgium Research programme: galantamine Sanochemia Pharmazeutika is investigating SPH 1285 Acetylcholinesterase inhibitors Alzheimer's disease Preclinical Unknown route Austria Sanochemia Pharmazeutika Originator Austria Pharmaceutical Public derivatives - Sanochemia galantamine derivatives as potential treatments SPH 1286 Dementia Preclinical Unknown route Austria, United Kingdom Sanochemia Pharmazeutika Owner Austria Pharmaceutical Public Pharmazeutika for various neurodegenerative disorders, including dementia, stroke, brain injury, SPH 1371 Neurological disorders Preclinical Unknown route Austria, United Kingdom Parkinson's disease, Alzheimer's disease and neuropathic pain. The company's most developed 128 molecule [SPH 1285] has a partially novel mechansim of action and is a candidate for phase I clinical trials. [CONT.] Research programme: galantamine Sanochemia Pharmazeutika is investigating Acetylcholinesterase inhibitors derivatives - Sanochemia galantamine derivatives as potential treatments Pharmazeutika for various neurodegenerative disorders, including dementia, stroke, brain injury, Parkinson's disease, Alzheimer's disease and neuropathic pain. The company's most developed SPH 1373 Neuropathic pain Preclinical Unknown route Austria 128 molecule [SPH 1285] has a partially novel SPH 1375 mechansim of action and is a candidate for SPH-1285 phase I clinical trials. [CONT.] SPH-1286 SPH-1371 SPH-1373 SPH-1375 SPH1285 Research programme: galantamine Galantos Pharma GmbH is developing an inactive Galantamine pro-drug - Galantos Pharma Acetylcholinesterase inhibitors Alzheimer's disease Preclinical Intranasal Germany Galantos Pharma Originator Germany Pharmaceutical Private prodrug - Galantos Pharma prodrug of galantamine, GLN 1062, for the treatment of Alzheimer's disease (AD). The prodrug is proposed to be an improved version of 129 the acetylcholinesterase inhibitor and nicotinic GLN 1062 Nicotinic receptor modulators Alzheimer's disease Preclinical IV Germany Galantos Pharma Owner Germany Pharmaceutical Private receptor modulator galantamine, which is GLN-1062 conventionally used for the treatment of mild-to- GLN1062 moderate AD [see separate profile for Memogain® galantamine]. [CONT.] Pro-galantamine - Galantos Pharma Research programme: gamma Merck & Co. is developing small molecule MRK 003 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public secretase inhibitors - Merck inhibitors of human amyloid precursor protein secretase (gamma-secretase) for the treatment of Alzheimer's disease (AD) and cancer. Various 130 classes of potent, functionally active gamma- secretase inhibitors have been discovered and characterised including benzodiazepine MRK 560 Notch signalling pathway inhibitors Cancer Preclinical PO USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public derivatives, aryl sulfones and [4.2.1]-bicyclo- MRK-003 based sulfonamides. [CONT.] MRK-560 Research programme: glutathione- to-BBB is developing therapeutics formulated 2B3 201 Immunosuppressants Inflammation Preclinical Unknown route Netherlands to-BBB technologies Originator Netherlands Biotechnology Private pegylated liposome therapeutics - to- using its proprietary glutathione-pegylated BBB liposomes for the treatment of Alzheimer's 2B3-201 Steroid receptor agonists Multiple sclerosis Preclinical Unknown route Netherlands VIB Originator Belgium Institution N/A disease, brain cancer and CNS disorders. 131 Brain-targeted liposomal methylprednisolone Undefined mechanism Alzheimer's disease Research Unknown route Netherlands Traditionally, targeting these indications has been difficult due to the existence of the blood- Glutathione pegylated liposomal Brain cancer Research Unknown route Netherlands brain barrier which impedes the access of many methylprednisolone therapeutic agents to the brain. [CONT.] CNS disorders Research Unknown route Netherlands Research programme: heat shock ALS Biopharma is developing brain-penetrant HSP70 heat shock protein inhibitors Alzheimer's disease Preclinical Unknown route USA ALS Biopharma Originator USA Biotechnology Private protein 70 inhibitors - ALS inducers of heat shock protein 70 (Hsp70), for Biopharma the treatment of neurodegenerative disorders such as Alzheimer's disease and amytrophic 132 lateral sclerosis (ALS). Hsp70 clears two proteins, the toxic form of tau protein and beta- amyloid, involved in disease progression. Development is at the preclinical stage in the US. Amyotrophic lateral sclerosis Preclinical Unknown route USA ALS Biopharma Owner USA Biotechnology Private Vybion Technology Provider USA Company Research programme: histamine H3 Ligand Pharmaceuticals is developing histamine Histamine H3 receptor antagonists Alzheimer's disease Preclinical Unknown route USA Ligand Pharmaceuticals Originator USA Biotechnology Public receptor antagonists - Ligand H3 antagonists for the treatment of sleep disorders (narcolepsy), attention deficit hyperactivity disorder (ADHD) and cognitive disorders (schizophrenia and Alzheimer's 133 disease). The H3 receptor modulates histamine release in the brain, controlling the release of excitatory neurotransmitters such as glutamate Attention-deficit hyperactivity disorder Preclinical Unknown route USA Ligand Pharmaceuticals Owner USA Biotechnology Public and acetylcholine by stimulating H1 receptors Narcolepsy Preclinical Unknown route USA [CONT.] Schizophrenia Preclinical Unknown route USA Research programme: histone EnVivo Pharmaceuticals is undertaking a EVX 001688 Histone deacetylase inhibitors Alzheimer's disease Preclinical PO Canada, USA CHDI Collaborator USA Biotechnology Private deacetylase inhibitors - EnVivo research programme to develop a series of small Pharmaceuticals molecule, orally available, histone deacetylase (HDAC) inhibitors for the treatment of neurodegenerative disorders, including 134 Parkinson's disease (PD), Huntington's disease (HD), dementia and Alzheimer's disease (AD). EVX001688 Huntington's disease Preclinical PO Canada, USA EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private These isotype-selective, brain-permeable HDAC HDAC inhibitors - EnVivo Neurodegenerative disorders Preclinical PO Canada, USA MethylGene Originator Canada Biopharmaceutical Public inhibitors have been exclusively in-licensed from HDACi - EnVivo Parkinson's disease Preclinical PO Canada, USA Mirati Therapeutics Owner USA Biopharmaceutical Public MethylGene which were generated using the Isotope-selective HDAC inhibitors (Series B) - company's HDAC technology [CONT.] EnVivo Research programme: homeostasis Coyote Pharmaceuticals is developing therapies CNS 101 Heat-shock protein stimulants Alzheimer's disease Preclinical Unknown route USA Coyote Pharmaceuticals Originator USA Biopharmaceutical Private modulators - Coyote Pharmaceuticals that modulate homeostasis for the treatment of diseases with large unmet medical needs in several therapeutic areas, including neurodegenerative, cardiovascular, oncology, CNS 102 Amyotrophic lateral sclerosis Preclinical Unknown route USA Coyote Pharmaceuticals Owner USA Biopharmaceutical Private 135 and inflammatory areas. The way that these CNS 101 therapies modulate homeostasis may include CNS 102 interactions with molecular chaperones, heat CNS-101 shock proteins, ubiquitin proteasomes, and DNA- CNS-102 RNA transcriptional regulators of homeostasis CNS101 network components [CONT.] CNS102 Research programme: Ig fusion Neurophage Pharmaceuticals is developing NPT-007 Alpha-synuclein modulators Alzheimer's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Originator USA Biotechnology GAIM dimers - NeuroPhage therapies targeted at protein misfolding. The Pharmaceuticals proprietary phage technology used results in products with a novel mechanism of action based on a general amyloid interaction motif (GAIM). 136 The motif is characteristic of distinctive, recurring NPT-014 Amyloid beta-protein modulators Parkinson's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Owner USA Biotechnology components of protein structures and interaction, NPT-088 Tau protein modulators including those of pathological protein NPT007 aggregates that are hallmarks of both NPT014 Alzheimer's and Parkinson's diseases [CONT.] NPT088 Research programme: imino sugar Summit Corporation plc (VASTox) is developing MNLP462a Glucose modulators Alzheimer's disease Preclinical PO United Kingdom MNLpharma Originator United Kingdom Pharmaceutical Private therapeutics - Summit orally available, small molecule imino sugar compounds for the treatment of Alzheimer's SMT 14400 Haemoglobin modulators Cancer No development reported(Preclinical) PO United Kingdom Summit plc Owner World Biotechnology Public disease. The compounds were also being developed for the treatment of hepatitis C, SMT C2100 Hepatitis C virus NS3 protein modulators Diabetes mellitus No development reported(Preclinical) PO United Kingdom diabetes mellitus and cancer, but no recent development has been reported in these SMT-14224 Hexosaminidase C inhibitors Viral infections No development reported(Preclinical) PO Europe 137 indications. [CONT.] SMT-14400 Immunomodulators Hepatitis C No development reported(Research) PO United Kingdom SMT-C2100 Immunostimulants SMT14224 Triglyceride modulators SMT14400 VOX 14400 VOX-14400 VOX14400 Research programme: BioArctic Neuroscience in Sweden is developing AD 0802 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral Sweden BioArctic Neuroscience Originator Sweden Biotechnology Private Immunotherapeutics - BioArctic immunotherapeutics, including monoclonal AD-0802 Amyloid beta-protein inhibitors Parkinson's disease Preclinical Parenteral Sweden BioArctic Neuroscience Owner Sweden Biotechnology Private Neuroscience antibodies and vaccines, for the treatment of AD0802 Immunomodulators Alzheimer's disease (AD) and Parkinson's disease Alzheimer's vaccine - BioArctic Neuroscience (PD). The company's proprietary technology BAN 2203 138 platform is used to isolate proteins implicated in BAN-2203 neurological disorders, such as beta-amyloid and BAN2203 alpha-synuclein, study their aggregation Monoclonal antibodies - BioArctic Neuroscience properties, prepare and stabilise other PD 0805 protofibrils, and develop protofibril specific PD-0805 monoclonal antibodies [CONT.] PD0805 Research programme: kinase Plexxikon (a Daiichi Sankyo subsidiary) is Omni-Raf inhibitors - Plexxikon Fms-like tyrosine kinase 3 inhibitors Alzheimer's disease Preclinical PO USA Plexxikon Originator USA Pharmaceutical Private inhibitors - Plexxikon developing a portfolio of orally-administered small-molecule kinase inhibitors. One focus of this programme appears to be inhibitors of Raf PLX FK1 Proto-oncogene protein b-raf modulators Cancer Preclinical PO USA Plexxikon Owner USA Pharmaceutical Private kinase (proto-oncogene protein b-raf-inhibitors) 139 PLX 7486 Raf kinase inhibitors Inflammation Preclinical PO USA as potential therapies for cancer. The programme is also investigating compounds that target Fms kinase for the treatment of cancer, Alzheimer's disease, and inflammatory diseases such as multiple sclerosis and lupus [CONT.] Research programme: kinase Plexxikon (a Daiichi Sankyo subsidiary) is inhibitors - Plexxikon developing a portfolio of orally-administered small-molecule kinase inhibitors. One focus of this programme appears to be inhibitors of Raf kinase (proto-oncogene protein b-raf-inhibitors) 139 as potential therapies for cancer. The programme PLX-FK1 TrkA receptor antagonists Multiple sclerosis Preclinical PO USA is also investigating compounds that target Fms PLX4720 TrkB receptor antagonists Polycystic kidney disease Preclinical PO USA kinase for the treatment of cancer, Alzheimer's PLX7486 TrkC receptor antagonists Solid tumours Preclinical PO USA disease, and inflammatory diseases such as PLX7486-TsOH Vascular endothelial growth factor receptor-1 multiple sclerosis and lupus [CONT.] antagonists Research programme: leptin - Neurotez is developing a hormone product Leptin - Neurotez AMP activated protein kinase modulators Alzheimer's disease Preclinical Parenteral USA National Institutes of Health (USA) Funder USA Institution N/A Neurotez candidate leptin for the treatment of Alzheimer's disease (AD) and other cognitive disorders. Leptin is a protein that is derived from adipocyte 140 hormone and has been linked in pathological pathways relevant to AD. In particular, it controls AMP-dependent kinase which regulates glycogen synthase kinase-3, which then modulates tau Amyloid beta-protein inhibitors Neurotez Originator USA Biotechnology Private phosphorylation. [CONT.] Neurotez Owner USA Biotechnology Private Research programme: liver X Vitae Pharmaceuticals is developing small VTP 4 Liver X receptor modulators Alzheimer's disease Preclinical PO USA Vitae Pharmaceuticals Originator USA Pharmaceutical Private receptor modulators - Vitae molecule liver X receptor (LXR) modulators for Pharmaceuticals the treatment of atherosclerosis and Alzheimer's disease. Discovery is based on Vitae's 141 CONTOUR® technology, a structure-based drug design platform which allows design and optimisation of compounds within the binding site of a target protein. [CONT.] VTP-4 Atherosclerosis Preclinical PO USA Vitae Pharmaceuticals Owner USA Pharmaceutical Private Research programme: M1 muscarinic Merck & Co. is developing selective M1 Muscarinic M1 receptor modulators Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public receptor modulators - Merck and Co. muscarinic positive allosteric receptor 142 modulators for the treatment of Alzheimer's disease. Development of the programme is at the Merck & Co Owner USA Large Pharma, Pharmaceutical Public preclinical stage in the US. Research programme: biOasis Technologies is developing BT 2111 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral Canada biOasis Technologies Originator USA Biotechnology Private melanotransferrin conjugated melanotransferrin (p97; CD228) as a carrier of therapeutics - biOasis Technologies therapeutic and imaging agents across the blood- brain barrier (BBB) for use in various indications, including brain metastases and Alzheimer's 143 disease. A melanotransferrin-trastuzumab BT 2211 Biological transport stimulants Brain metastases Preclinical Parenteral Canada biOasis Technologies Owner Canada Biotechnology Private (Herceptin®) conjugate, known as BT 2111, is BT-2111 Enzyme replacements Lysosomal storage diseases Preclinical IV Canada Texas Tech University Health Sciences Center Collaborator USA University N/A undergoing preclinical studies for the treatment BT-2211 Transferrin receptor modulators University of British Columbia Originator Canada University N/A of HER2+ brain cancer that has metastasised BT2111 from primary breast cancer, in Canada [CONT.] BT2211 Herceptin®-BT2111 Research programme: membrane D-Pharm in Israel is developing small molecule, DP 460 Chelating agents Alzheimer's disease Preclinical PO Israel D-Pharm Originator Israel Pharmaceutical Private active metal ion chelators - D-Pharm lipophilic, membrane activated, transition-metal ion chelators for the treatment of Alzheimer's disease. 144 The company has selected a lead compound, DP-460 Amyotrophic lateral sclerosis Discontinued(Preclinical) PO Israel D-Pharm Owner Israel Pharmaceutical Private called DP 460. DP 460, a derivative of the calcium chelator BAPTA, showed selective membrane-dependent modulation of copper and zinc homeostasis. [CONT.]

Research programme: metabotropic Addex Therapeutics (formerly Addex ADX 47273 Metabotropic glutamate receptor 5 modulators Alzheimer's disease Preclinical PO Switzerland Addex Pharmaceuticals Originator Switzerland Pharmaceutical Public glutamate receptor 5 modulators - Pharmaceuticals) is evaluating positive and ADX 50938 Cognition disorders Preclinical PO Switzerland Addex Therapeutics Owner Switzerland Pharmaceutical Public Addex Therapeutics negative allosteric metabotropic glutamate ADX 63365 Schizophrenia Preclinical PO Switzerland receptor-5 (mGluR5) modulators for potential ADX47273 application in schizophrenia, Alzheimer's disease ADX50938 145 and other cognitive disorders. Allosteric ADX63365 (mGluR5 PAMb) modulators are a novel class of small-molecule, ADX63365 (mGluR5 positive allosteric modulator oral drug candidates with a chemical structure [PAM]) unrelated to that of competitive agonist or CDPPB Metabotropic glutamate receptor-5 modulators - antagonist drugs [CONT.] Addex mGluR5 modulators - Addex Research programme: metal-protein- Prana Biotechnology is undertaking a research MPAC - Prana Biotechnologies Alpha-synuclein inhibitors Age-related macular degeneration Preclinical Unknown route Australia Prana Biotechnology Originator Australia Biotechnology Public attenuating compounds - Prana programme to develop disease-modifying agents PBT 434 Chelating agents Alzheimer's disease Preclinical Unknown route Australia Prana Biotechnology Owner Australia Biotechnology Public Biotechnology derived from its proprietary metal-protein- PBT-434 Iron chelating agents Parkinson's disease Preclinical PO Australia The Michael J. Fox Foundation for Parkinsons Research Funder USA Institution N/A 146 attenuating compound (MPAC) library for the treatment of Alzheimer's disease, Parkinson's PBT3 series - Prana Biotechnologies disease (PD), and possibly age-related macular PBT4 series - Prana Biotechnologies degeneration (AMD). [CONT.] PBT434 Research programme: monoclonal Intellect Neurosciences is using its proprietary 1A10 Amyloid beta-protein inhibitors Age-related macular degeneration Preclinical Parenteral USA Immuno-Biological Laboratories Originator Japan Company antibodies and antibody-drug Antisenilin® passive immunisation technology to 8,20E+02 Amyloid inhibitors Alzheimer's disease Preclinical IV USA Intellect Neurosciences Licensee USA Biopharmaceutical Public conjugates - Intellect Neurosciences develop monoclonal antibodies that target beta- Anti-Abeta monoclonal antibodies Antioxidants Alzheimer's disease Preclinical Parenteral USA MRC Technology Technology Provider United Kingdom Company amyloid (Abeta) protein for the treatment of Alzheimer's disease (AD). The company licensed IN N01 Protein aggregation inhibitors Glaucoma Preclinical Parenteral USA Northwestern University Originator USA University N/A 147 two Abeta-specific monoclonal antibodies, 82E1 IN-N01 Tau protein inhibitors (IN N01) and 1A10, from Immuno-Biological IN-N01-OX2 Laboratories (IBL). [CONT.] N01-OX2 T01-OX2 tauC3 TOC 1 TOC-1 Research programme: muscarinic Mithridion (formerly Cognitive Pharmaceuticals) CDD 0097 Muscarinic M1 receptor agonists Alzheimer's disease Preclinical Unknown route USA Mithridion Licensee USA Biopharmaceutical receptor agonists - Mithridion in the US is developing small molecule, CDD 0098J Muscarinic receptor agonists Schizophrenia Preclinical Unknown route USA University of Toledo Originator USA University N/A muscarinic receptor agonists for the treatment of CDD 0199J University of Toledo Owner USA University N/A various central nervous system (CNS) disorders, CDD 0304 particularly schizophrenia and associated CDD 0312 cognitive deficits. The muscarinic programme CDD 0313 was originated by the University of Toledo, which CDD 0314 licensed it to Cognitive Pharmaceuticals (later CDD 0316 Mithridion). [CONT.] CDD 0317 CDD 0322 148 CDD-0097 CDD-0098J CDD-0199J CDD-0304 CDD-0312 CDD-0313 CDD-0314 CDD-0316 CDD-0317 CDD-0322 MI 10 022 MI-10-022 Research programme: Nanobodies - Boehringer Ingelheim and Ablynx are Undefined mechanism Alzheimer's disease Preclinical Parenteral Belgium, Germany Ablynx Originator Belgium Biopharmaceutical Private Ablynx/Boehringer Ingelheim collaborating in the development of Nanobodies®, a class of therapeutic proteins, for potential use in the treatment of Alzheimer's disease (AD), autoimmune disorders, cancer, and 149 respiratory disorders. Nanobodies® are antibody- derived proteins developed by Ablynx which contain novel structural and functional properties Autoimmune disorders Preclinical Parenteral Belgium, Germany Boehringer Ingelheim Originator Germany Large Pharma, Pharmaceutical Private of naturally-occurring heavy-chain antibodies Cancer Preclinical Parenteral Belgium, Germany [CONT.] Respiratory tract disorders Preclinical Parenteral Belgium, Germany Research programme: Neuronascent is developing a series of chemically NNI 362 Alzheimer's disease Preclinical PO USA Neuronascent Originator USA Biotechnology Private neurodegenerative disease diverse neurogenic compounds as disease- therapeutics - Neuronascent modifying drugs for the treatment of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease. The 150 neurogenic agents are designed to enable replacement of damaged neurons in key areas of the brain through stimulation of neurogenesis NNI 370 Parkinson's disease Research PO USA Neuronascent Owner USA Biotechnology Private (i.e. nerve cell growth) and enhancement of NNI-362 neuroprotection [CONT.] Research programme: Neuronascent is developing a series of chemically neurodegenerative disease diverse neurogenic compounds as disease- therapeutics - Neuronascent modifying drugs for the treatment of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease. The 150 neurogenic agents are designed to enable replacement of damaged neurons in key areas of the brain through stimulation of neurogenesis (i.e. nerve cell growth) and enhancement of neuroprotection [CONT.] NNI-370 Research programme: UK-based pharmaceutical company Phytopharm PYM 60086 Nerve growth factor stimulants Alzheimer's disease Preclinical PO United Kingdom Phytopharm Originator England Pharmaceutical Public neurodegenerative disease is developing botanical-based pharmaceuticals therapeutics - Phytopharm for the treatment of dementia including Alzheimer's disease (programme P58), Parkinson's disease (programme P63), vascular 151 dementia and age-related memory impairment. Additional indications include diabetic neuropathy and neuropsychiatric disorders, such as PYM60086 Cognition disorders Preclinical PO United Kingdom Phytopharm Owner England Pharmaceutical Public schizophrenia, depression, anxiety and epilepsy. Dementia Preclinical PO United Kingdom [CONT.] Memory disorders Preclinical PO China Research programme: ProteoTech is developing proprietary, small DP 68 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Intranasal USA ProteoTech Originator USA Biotechnology Private neurodegenerative disease molecules for the potential use in therapeutics - ProteoTech neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Drug DP 74 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO USA ProteoTech Owner USA Biotechnology Private classes that have emerged from this programme 152 DP-68 Parkinson's disease Preclinical PO USA include small molecules and peptides that reduce DP-74 and/or trigger clearance of amyloid-beta (Abeta) PeptiClere™ for AD and molecules targeting the formation and PTI 777 persistence of alpha-synuclein in PD [CONT.] PTI-777 Synuclere™ Research programme: TauTaTis is undertaking a research programme TTT 3002 LRRK2 protein inhibitors Alzheimer's disease Preclinical PO USA TauTaTis Originator USA Pharmaceutical Private neurodegenerative disorder to discover and develop a series of proprietary therapeutics - TauTaTis and orally bioavailable, small molecules as multi- targeted kinase inhibitors for the treatment of Alzheimer's disease (AD), Parkinson's disease 153 (PD) and cancer. Such compounds uniquely affect various targets, which are relevant for several disease processes, thereby, offer a disease-modifying strategy versus one solely for TTT-3002 Protein kinase inhibitors Cancer Preclinical PO USA TauTaTis Owner USA Pharmaceutical Private symptomatic relief [CONT.] Tau protein modulators Parkinson's disease Preclinical PO USA Research programme: BioChromix Pharma has a research programme Alzheimer's disease Preclinical Unknown route Sweden BioChromix Pharma Originator Sweden Pharmaceutical Private neurodegenerative disorders investigating therapeutics for the treatment of therapeutics - BioChromix Pharma neurodegenerative disorders. The company's 154 initial focus is on Alzheimer's disease. Lead compounds based on proprietary polymer technology are in preclinical investigation. BioChromix Pharma Owner Sweden Pharmaceutical Private Research programme: KineMed and Bristol-Myers Squibb are developing Undefined mechanism Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public neurodegenerative disorders therapeutics for the treatment of Alzheimer's therapeutics - KineMed/Bristol- disease and other neurodegenerative disorders. 155 Myers Squibb KineMed will utilise their stable isotope technology to aid in drug discovery. Preclinical development is ongoing in the US. Neurodegenerative disorders Preclinical Unknown route USA KineMed Originator USA Biotechnology Private Research programme: Oryzon is developing small molecule therapeutics ORY 2001 Lysine specific demethylase 1 modulators Huntington's disease Preclinical Unknown route Spain Oryzon Originator Spain Biotechnology Private neurodegenerative disorders for the treatment of neurodegenerative disorders, therapeutics - Oryzon such as Alzheimer's disease (AD), Parkinson's disease (PD), dementia, and Huntington's 156 disease (HD). The research programme focuses on targeting lysine specific demethylase 1 (LSD1), which plays a role in regulating the ORY-2001 Monoamine oxidase B inhibitors Alzheimer's disease Research Unknown route Spain Oryzon Owner Spain Biotechnology Private expression of crucial genes that support neuron Dementia Research Unknown route Spain viability. [CONT.] Parkinson's disease Research Unknown route Spain Research programme: PharmaNeuroBoost N.V. of Belgium is PNB 03 Alzheimer's disease Preclinical Unknown route Belgium PharmaNeuroBoost Originator Belgium Pharmaceutical Private neurodegenerative disorders undertaking a research programme to develop therapeutics - PharmaNeuroBoost compounds for the treatment of neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). Lead candidates are undergoing preclinical 157 development for AD and PD. Two lead candidates to emerge is PNB 03 and PNB 04 Parkinson's disease Preclinical Unknown route Belgium PharmaNeuroBoost Owner Belgium Pharmaceutical Private PNB 04, which are undergoing IND-enabling studies for PD and AD, respectively.

PNB03 PNB04 Research programme: The US company Samaritan Pharmaceuticals is Caprospinol Acetylcholinesterase inhibitors Alzheimer's disease Preclinical PO Canada Advinus Therapeutics Collaborator India CRO Private neurodegenerative disorders collaborating with McGill University in Canada in SP 04 Amyloid beta-protein inhibitors Huntington's disease Preclinical PO USA CHDI Collaborator USA Biotechnology Private therapeutics - Samaritan/McGill the discovery and development of therapeutics SP 04m Sigma-1 receptor antagonists Georgetown University Originator USA University N/A University for the treatment of neurodegenerative disorders SP 08 McGill University Originator Canada University N/A such as Alzheimer's disease (AD) and SP 233 Samaritan Pharmaceuticals Originator USA Biopharmaceutical Public 158 Huntington's disease (HD). Certain compounds in SP-004 this programme (such as caprospinol) inhibit SP-008 beta-amyloid and others (such as SP 04) inhibit SP-04 acetylcholinesterase and the sigma-1 receptor SP-04m [CONT.] SP-08 SP-233 Research programme: neurogenesis NeuroNova AB is engaged in the discovery and sNN 0126 Neuron stimulants Alzheimer's disease Preclinical Unknown route Sweden Genentech Technology Provider USA Large Pharma, Biotechnology Public therapeutics - NeuroNova AB development of small molecule drugs that promote neurogenesis (i.e. the formation of new sNN 0465 Neuropilin-1 inhibitors Amyotrophic lateral sclerosis Preclinical Intracerebro ventricular Sweden NeuroNova AB Originator Sweden Biopharmaceutical Private neurons) via activity on neural stem and progenitor cells for the treatment of CNS sNN0126 Platelet derived growth factor BB modulators Huntington's disease Preclinical Unknown route Sweden NeuroNova AB Owner Sweden Biopharmaceutical Private disorders, including Parkinson's disease (PD), 159 Alzheimer's disease (AD), Huntington's disease sNN0465 Stem cell stimulants Major depressive disorder Preclinical Unknown route Sweden (HD), amyotrophic lateral sclerosis (ALS) and Neurological disorders Preclinical Intracerebro ventricular Sweden depression. [CONT.] Neurological disorders Preclinical PO Sweden Parkinson's disease Preclinical Intracerebro ventricular Sweden

Research programme: neurological Affichem is developing therapeutics for disorders AF 243 Cell differentiation stimulants Hearing loss Preclinical Otic France Affichem Originator France Biotechnology Private disorder therapeutics - Affichem with neurological involvement including; hearing loss, Parkinson's disease, Alzheimer's disease, retinal disorders (retinopathy) and medullary 160 lesions. A lead candidate, AF 243, is undergoing AF 250s Neuron modulators Parkinson's disease Preclinical Unknown route France Affichem Owner France Biotechnology Private preclinical development. Early research is also AF243 Alzheimer's disease Research Unknown route France being conducted on another candidate known as AF250s Brain injuries Research Unknown route France AF 250s. [CONT.] Retinal disorders Research Ophthalmic France Research programme: neurological Australia-based Neurosciences Victoria is Undefined mechanism Alzheimer's disease Preclinical Unknown route Australia Neurosciences Victoria Originator Australia Technology Transfer Private disorder therapies - Neurosciences conducting research into several neurological Victoria disorders, with the aim of discovering potential therapeutics. The company's areas of research Amyotrophic lateral sclerosis Preclinical Unknown route Australia Neurosciences Victoria Owner Australia Technology Transfer Private 161 include epilepsy, stroke, neurodegenerative Epilepsy Preclinical Unknown route Australia disorders, primarily Alzheimer's disease, Multiple sclerosis Preclinical Unknown route Australia Parkinson's disease and amyotrophic lateral Neurological disorders Preclinical Unknown route Australia sclerosis, and glial cell disorders, particularly Parkinson's disease Preclinical Unknown route Australia multiple sclerosis (MS). [CONT.] Stroke Preclinical Unknown route Australia Research programme: neurological Arrien Pharmaceuticals is developing orally ORS 1006 DYRK kinase inhibitors Alzheimer's disease Preclinical PO USA Arrien Pharmaceuticals Collaborator USA Pharmaceutical Private disorders kinase inhibitors - Arrien administered, small molecule inhibitors of protein Pharmaceuticals kinases for the treatment of Alzheimer's disease (AD), Parkinson's disease (PD) and Down 162 syndrome. These compounds were originated by Oros Pharmaceuticals, and are being developed with Arrien's proprietary Fragment-Field Drug ORS 1104 LRRK2 protein inhibitors Down syndrome Preclinical PO USA Oros Pharmaceuticals Originator India Manufacturer Design (FFDD)™ technology platform. [CONT.] ORS-1006 Parkinson's disease Preclinical PO USA Oros Pharmaceuticals Owner India Manufacturer ORS-1104 Research programme: neuronal stem Samaritan Pharmaceuticals in the US is SP sc4 Stem cell stimulants Alzheimer's disease Preclinical Unknown route Canada CHDI Licensee World Biotechnology Private cell therapeutics - Samaritan/McGill collaborating with McGill University in Canada in University the discovery and development of small molecule 163 compounds that induce neural stem cell SP sc7 Huntington's disease Preclinical Unknown route USA Georgetown University Originator USA University N/A differentiation, as potential treatments of various SP-sc4 Neurodegenerative disorders Preclinical Unknown route Canada McGill University Originator Canada University N/A neurodegenerative disorders. [CONT.] SP-sc7 Samaritan Pharmaceuticals Originator USA Biopharmaceutical Public Research programme: Bionure is developing neuroprotectants for the BN 201 TrkA receptor agonists Glaucoma Preclinical Ophthalmic Spain Bionure Originator Spain Biotechnology Private neuroprotectants - Bionure treatment of neurological and ophthalmological indications, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, glaucoma and acute optic neuritis. A lead 164 BN-201 TrkB receptor agonists Multiple sclerosis Preclinical IV Spain Bionure Owner Spain Biotechnology Private candidate from this programme is BN 201 (also BN201 Multiple sclerosis Preclinical PO Spain known as G 79), a first-in-class peptoid G 79 Optic neuritis Preclinical IV Spain neuroprotectant that works by binding to the G-79 Alzheimer's disease Research IV Spain extracellular portion of TrkA and TrkB and G79 Amyotrophic lateral sclerosis Research IV Spain activating the neurotrophin pathway [CONT.] Parkinson's disease Research IV Spain Research programme: Allon Therapeutics (a subsidiary of Paladin Labs) ADNF-9 Neuron stimulants Alzheimer's disease Preclinical Unknown route Canada Allon Therapeutics Originator Canada Biotechnology Public neuroprotective therapies - Allon has a research programme aimed at developing AL 209 Tubulin modulators Fetal alcohol syndrome Preclinical Unknown route Canada Paladin Labs Owner Canada Pharmaceutical Public Therapeutics neuroprotective compounds derived from its two AL 309 Neuroprotection Preclinical PO USA technology platforms, Activity-Dependent AL 408 Peripheral nervous system diseases Preclinical PO Canada Neurotrophic Factor (ADNF) and Activity- AL 508 Peripheral nervous system diseases Preclinical SC Canada Dependent Neuroprotective Protein (ADNP), for AL-209 Peripheral nervous system diseases (Chemotherapy- Preclinical PO France 165 the treatment of degenerative diseases and induced:oxaliplatin induced peripheral neuropathy) injuries. [CONT.] AL-309 Eye disorders No development reported(Preclinical) Unknown route Germany, Israel

AL-408 AL-508 SAL SALLRSIPA Research programme: NGF-based Lay Line Genomics is developing proprietary Neuron stimulants Alzheimer's disease Preclinical Intranasal Italy Lay Line Genomics Originator Italy Biopharmaceutical Private Alzheimer's disease therapy - Lay formulations of nerve growth factor (NGF) Line Genomics coupled to a diagnostic system for the non- 166 invasive treatment of Alzheimer's disease. An intranasal formulation of NGF is undergoing proof- of-principle, preclinical studies in Italy. [CONT.] Lay Line Genomics Owner Italy Biopharmaceutical Private Research programme: NMDA Naurex is developing peptides and synthetic NRX 1050 NMDA receptor modulators Alzheimer's disease Preclinical PO USA Naurex Originator USA Biopharmaceutical Private receptor modulators - Naurex small molecules as modulators of the N-methyl-D- NRX 1051 Autistic disorder Preclinical PO USA Naurex Owner USA Biopharmaceutical Private aspartate (NMDA) receptor for the treatment of NRX 1059 Major depressive disorder Preclinical IV USA major depressive disorder, schizophrenia, NRX 105x Major depressive disorder Preclinical PO USA Alzheimer's disease, neuropathic pain and NRX 1060 Neuropathic pain Preclinical PO USA autistic disorder. In preclinical trials, NMDA NRX 2085 Schizophrenia Preclinical IV USA 167 modulators have exhibited therapeutic activity NRX 20xx Schizophrenia Preclinical PO USA without the limiting side effects, such as NRX-1050 dissociative effects and sedation, commonly NRX-1051 observed with other compounds targeting the NRX-1059 NMDA receptor [CONT.] NRX-105x NRX-1060 NRX-2085 NRX-20xx Research programme: nuclear Genfit is developing compounds that target AD Inov collaborative programme Cytoplasmic and nuclear receptor modulators Alzheimer's disease Preclinical Unknown route France Genfit Originator France Biopharmaceutical Public receptor-targeting therapeutics - various nuclear receptors for the treatment of Genfit Alzheimer's disease, cardiometabolic disorders and autoimmune disorders. Drug candidates include G 15750, a selective peroxisome 168 G-15750 Nuclear receptor subfamily 1 group F member 3 Cardiovascular disorders Preclinical Unknown route France Genfit Owner France Biopharmaceutical Public proliferator-activated receptor modulator. Genfit antagonists has two programmes, TGFTX1 and TGFTX3, G15750 Peroxisome proliferator-activated receptor Metabolic disorders Preclinical Unknown route France which target nuclear receptors that are involved modulators in the circadian rhythm (Rev-Erbalpha and TGFTX1 Autoimmune disorders Research Unknown route France RORalpha/RORgamma) [CONT.] TGFTX3 Research programme: peptide-based RAPID Pharmaceuticals is developing small RAP 103 CCR2 receptor antagonists Alzheimer's disease Preclinical PO USA McGill University Collaborator Canada University N/A therapeutics - RAPID stable peptides for the treatment of Alzheimer's RAP 160 CCR3 receptor antagonists Hepatitis B Preclinical PO Germany, USA RAPID Pharmaceuticals Originator Switzerland Biotechnology Private Pharmaceuticals disease (RAP 310), chronic hepatitis B (RAP RAP 163 CCR5 receptor antagonists Neuropathic pain Preclinical PO Canada, USA RAPID Pharmaceuticals Owner Switzerland Biotechnology Private 164), neuropathic pain (RAP 103), ovarian RAP 164 Chemokine receptor antagonists Prostate cancer Preclinical PO USA University of Duisburg-Essen Collaborator Germany University N/A cancer (RAP 701), prostate cancer (RAP 163) RAP 310 Chemokine receptor modulators Psoriasis Preclinical PO USA University of Michigan Collaborator USA University N/A 169 and psoriasis (RAP 160). The company has RAP 701 Immunostimulants Ovarian cancer Research PO USA stated that these compounds, which target RAP103 Stem cell inhibitors specific chemokine receptors, represent a fourth RAP160 generation of peptide development. [CONT.] RAP163 RAP164 RAP310 RAP701 Research programme: PET imaging FluoroPharma is developing positron emission [18F]AppCHFppA Positron-emission tomography enhancers Atherosclerosis (Diagnosis) Preclinical Parenteral USA FluoroPharma Licensee USA Biopharmaceutical Private agents - FluoroPharma tomography (PET) imaging agents for use in the diagnosis of atherosclerosis, coronary disorders and Alzheimer's disease. The imaging agents under evaluation consist of molecules labelled with the 18F radioactive isotope. One lead 170 preclinical candidate, VasoPET or p2,p3- [18F]monofluoromethylene diadenosine-5',5'''- p1,p4-tetraphosphate ([18F]AppCHFppA), is a purine analogue that targets active adenosine phosphate molecule receptors, which are associated with inflammatory conditions [CONT.] AZPET Coronary disorders (Diagnosis) Preclinical Parenteral USA Harvard Medical School Originator USA University N/A VasoPET Alzheimer's disease (Diagnosis) Research Parenteral USA Massachusetts General Hospital Originator USA Hospital N/A Research programme: PPAR GlaxoSmithKline is developing modulators for the GSK3787 Peroxisome proliferator-activated receptor Alzheimer's disease Preclinical PO USA GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public modulators - GlaxoSmithKline three known peroxisome proliferator-activated modulators receptor (PPAR) subtypes alpha, gamma and delta, for the potential treatment of cancer, type GW 0742 Cancer Preclinical Unknown route USA GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public 2 diabetes and Alzheimer's disease (AD). GW0742 Diabetes mellitus Preclinical Unknown route USA Preclinical studies of a series of compounds are 171 PPAR agonists research programme - Lipid metabolism disorders No development reported(Preclinical) Unknown route USA underway in the US. A PPARdelta agonist, GW GlaxoSmithKline 0742, has been tested in a mice model of AD. A PPARpan Metabolic syndrome No development reported(Preclinical) Unknown route USA PPAR beta/delta antagonist, GSK 3787, has also been evaluated in the treatment of cancer. PPARpan™ [CONT.] Research programme: PPARpan agonists - GlaxoSmithKline Research programme: progranulin Neurodyn is developing a neuroprotectant, called ND 602 Nerve tissue protein stimulants Alzheimer's disease Preclinical Unknown route Canada Neurodyn Originator Canada Biotechnology stimulants - Neurodyn ND 602, for the treatment of Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). ND 602 is designed to target 172 synthesis of progranulin, a multifunction protein expressed by neurons and microglia. Progranulin is thought to be involved in neuronal survival and ND-602 Amyotrophic lateral sclerosis Preclinical Unknown route Canada Neurodyn Owner Canada Biotechnology CNS inflammatory processes [CONT.] Parkinson's disease Preclinical Unknown route Canada Spinal muscular atrophy Preclinical Unknown route Canada Research programme: protein NeuroPhage Pharmaceuticals is developing NPT 001 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral USA NeuroPhage Pharmaceuticals Originator USA Biotechnology aggregation inhibitors - NeuroPhage therapeutics for the treatment of Pharmaceuticals neurodegenerative disease, including Alzheimer's disease and Parkinson's disease. The company is 173 using its proprietary protein disaggregation NPT 002 - NeuroPhage Amyloid beta-protein inhibitors Parkinson's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Owner USA Biotechnology technology targeting both beta-amyloid (Abeta) NPT-001 Tau protein inhibitors and tau proteins as a disease-modifying NPT-002 - NeuroPhage approach in the treatment of Alzheimer's disease. NPT001 [CONT.] NPT002 - NeuroPhage Research programme: protein Neotope Biosciences (a wholly-owned subsidiary NEOD002 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral Ireland Neotope Biosciences Originator United Kingdom Biopharmaceutical Public aggregation inhibitors - Prothena of Elan Corporation) initiated the development of Corporation monoclonal antibodies that modulate neo-epitope amyloid related targets, alpha synuclein and tau protein. These compounds could potentially be 174 used for the treatment of a range of neurodegenerative disorders including primary (AL) amyloidosis, Lewy body dementia, Amyloid inhibitors Amyloidosis Preclinical Parenteral Ireland Prothena Corporation Owner Ireland Biotechnology Public Parkinson's disease and Alzheimer's disease Protein aggregation inhibitors Neurodegenerative disorders Preclinical Parenteral Ireland [CONT.] Tau protein inhibitors Parkinson's disease Preclinical Parenteral Ireland Research programme: protein Signum Biosciences is using its proprietary SIG 1012 Protein phosphatase 2A modulators Alzheimer's disease Preclinical PO USA GlaxoSmithKline (China) Investment Co. Licensee China Pharmaceutical Public phosphatase 2A modulators - Phosphatase plaform to develop small molecule, GlaxoSmithKline/Signum orally active protein phosphatase 2A (PP2A) Biosciences modulators for the treatment of Alzheimer's 175 disease, Parkinson's disease, and type 2 diabetes mellitus. GlaxoSmithKline (China) is collaborating SIG 1106 Parkinson's disease Research PO USA Princeton University Technology Provider USA University N/A with Signum on the research and development in SIG1012 Type 2 diabetes mellitus Research PO USA Signum Biosciences Originator USA Biotechnology Private Alzheimer's disease. Development is at the SIG1033 Signum Biosciences Owner USA Biotechnology Private preclinical stage in the US. SIG1106 Research programme: RAGE AbbVie and CSL Behring are developing A 992400 Advanced glycosylation end-product receptor Alzheimer's disease Preclinical Parenteral Germany Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public monoclonal antibodies: AbbVie/CSL monoclonal antibodies (mABs) to receptor for antagonists Behring advanced glycation-end-products (RAGE) for the treatment of Alzheimer's disease (AD). RAGE is 176 thought to be a receptor for amyloid-beta (Abeta) and other ligands such as S100B, potentially contributing to AD disease A 992401 AbbVie Owner USA Biopharmaceutical Public progression. It is overexpressed in the brain A-992400 CSL Behring Originator USA Biopharmaceutical Public microvasculature of patients with AD. [CONT.] A-992401 CSL Behring Owner USA Biopharmaceutical Public Research programme: Rho GTP- ExonHit Therapeutics is utilising its Differential EHT 0101 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route France ExonHit Therapeutics Originator France Technology provider Public binding protein inhibitors - ExonHit Analysis of Transcripts with Alternative Splicing Therapeutics (DATAS™) technology to develop small molecule inhibitors of rho GTP-binding proteins (GTPases) for the treatment of cancer and Alzheimer's 177 disease. Rho GTP-binding proteins are involved in regulation of actin organisation, gene expression EHT 0206 GTP phosphohydrolase inhibitors Cancer Preclinical Unknown route France ExonHit Therapeutics Owner France Technology provider Public and cell cycle expression. Preclinical studies are EHT 101 Ras signal transduction pathway inhibitors Chronic myeloid leukaemia Preclinical Unknown route France being conducted by ExonHit in France. [CONT.] EHT 1864 Rho GTP-binding protein-inhibitors EHT 206 Research programme: rivastigmine A transdermal formulation of rivastigmine is Acetylcholinesterase inhibitors Alzheimer's disease Preclinical Transdermal South Korea Samyang Biopharmaceuticals Corporation Originator South Korea Pharmaceutical transdermal - Samyang being developed by Samyang Biopharmaceuticals Corporation (a division of Samyang Group) for the treatment of Alzheimer's disease. The 178 transdermal delivery technology applied by the company is designed to provide extended-release of drug into the patient's system, and holds the advantage of bypassing first pass metabolism. [CONT.] Butyrylcholinesterase inhibitors Samyang Group Originator South Korea Pharmaceutical Public Research programme: S- Merck & Co is developing orally bioavailable S- L 002259713 Adenosylhomocysteinase inhibitors Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public adenosylhomocysteine hydrolase adenosylhomocysteine hydrolase (AHCY) inhibitors - Merck & Co inhibitors for the treatment of Alzheimer's disease. Development is at the preclinical stage 179 in the US. Homocysteine is produced by the conversion of S- L-002259713 Merck & Co Owner USA Large Pharma, Pharmaceutical Public adenosylhomocysteine via the AHCY cytosolic enzyme to homocysteine and adenosine. [CONT.]

Research programme: selective Suven Life Sciences is developing potent and SUVN-F90101 Nicotinic receptor agonists Alzheimer's disease Preclinical Unknown route India Suven Life Sciences Originator India Company nicotinic acetylcholine receptor selective nicotinic acetylcholine alpha4beta2 agonists - Suven Life Sciences receptor agonists for the treatment of neurological disorders. SUVN F91201 has been 180 identified as a lead candidate for the treatment of Alzheimer's disease, and SUVN F90101 is the lead candidate for the treatment of neuropathic pain. Preclinical development is underway in India. SUVN-F91201 Neuropathic pain Preclinical Unknown route India Suven Life Sciences Owner India Company Research programme: serine Abide Therapeutics and the University of Hydrolase inhibitors Alzheimer's disease Preclinical Unknown route USA Abide Therapeutics Originator USA Biotechnology Private hydrolase inhibitors - Abide California, San Diego are collaborating on the Therapeutics/University of California development of small-molecule inhibitors of monoacylglycerol lipase (MAGL), a serine hydrolase, as potential therapies for Down 181 syndrome and Alzheimer's disease. The compounds were created by application of Abide Therapeutics' selective targeting technology. Initially, the researchers will assess the agents in an animal model of Down syndrome. [CONT.] Down syndrome Preclinical Unknown route USA University of California, San Diego Originator USA University N/A Research programme: serotonin 4 Suven Life Sciences is developing orally SUVN D1003019 Serotonin 4 receptor agonists Alzheimer's disease Preclinical PO India Suven Life Sciences Originator India Company receptor agonists - Suven Life bioavailable, selective serotonin 4 receptor Sciences (5HT4) agonists for the treatment of Alzheimer's disease. 5-HT4 receptor is expressed at a high 182 density in the limbic system including the hippocampus and frontal cortex, suggesting a role of this sub-type of 5-HT receptors in conditions associated with memory and cognition impairments. [CONT.] SUVN-D1003019 Suven Life Sciences Owner India Company Research programme: serotonin 6 AbbVie (formerly Abbott laboratories) is A 964324 Serotonin 6 receptor antagonists Alzheimer's disease Preclinical Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public receptor antagonists - AbbVie researching serotonin-6 (5HT6) receptor antagonists for their potential in the treatment of cognitive deficits in Alzheimer's disease and 183 schizophrenia in the US. Lead candidate A 964324 is a highly selective serotonin-6 receptor antagonist in in vitro and in vivo studies. A-964324 Schizophrenia Preclinical Unknown route USA AbbVie Owner USA Biopharmaceutical Public Preclinical development is ongoing in the US. A964324 [CONT.] Research programme: serotonin 6 Suven Life Sciences is developing orally active, SUVN-501 Serotonin 6 receptor antagonists Alzheimer's disease Preclinical PO India Suven Life Sciences Originator India Company receptor antagonists - Suven Life selective serotonin 6 (5-HT6) receptor Sciences antagonists, including tetrahydro carbazole derivatives, for the treatment of various cognition 184 disorders such as Alzheimer's disease and SUVN-504 Cognition disorders Preclinical PO India Suven Life Sciences Owner India Company schizophrenia, as well as obesity. SUVN 501, SUVN-507 Obesity Preclinical PO India SUVN 504, SUVN 507 (and its active metabolite, SUVN-623 Parkinson's disease Preclinical PO India M1), SUVN 901 and SUVN 976 are in preclinical SUVN-901 Schizophrenia Preclinical PO India development in India. [CONT.] SUVN-976 Research programme: serotonin 6 Wyeth (Pfizer) is developing serotonin 6 (5-HT6) 321348 Serotonin 6 receptor antagonists Alzheimer's disease Preclinical PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public receptor antagonists - Wyeth receptor antagonists for the oral treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease. Serotonin 6 receptor antagonists may improve deficits in 185 learning and memory by increasing levels of the neurotransmitters acetylcholine and glutamate. A series of arylsulfonyl compounds has been developed with optimised pharmacodynamic 5-HT6 receptor antagonists - Wyeth Wyeth Originator USA Large Pharma, Pharmaceutical Public properties [CONT.] WAY 101 WAY-101 Research programme: small Antoxis, an Aberdeen-based biotechnology Free radical modulators Alzheimer's disease Preclinical Unknown route Scotland Antoxis Originator United Kingdom Biotechnology molecule therapeutics - Antoxis company, is developing small molecule flavonoid therapeutics for the treatment of neurodegenerative disorders, such as Parkinson's 186 and Alzheimer's diseases, cardiovascular Cancer Preclinical Unknown route Scotland Antoxis Owner United Kingdom Biotechnology disorders, diabetes, and certain cancers. Flavonoids are polyphenolic phytochemicals that Cardiovascular disorders Preclinical Unknown route Scotland are found in a variety of foods and beverages. Diabetes mellitus Preclinical Unknown route Scotland [CONT.] Parkinson's disease Preclinical Unknown route Scotland Research programme: small Probiodrug AG is engaged in a research Cyclin dependent kinase 9 inhibitors Alzheimer's disease Preclinical PO Germany Evotec AG Collaborator Germany Pharmaceutical Public molecule therapeutics - Probiodrug programme focussed on the identification of orally active compounds for selectively modifying enzymatic activity, as potential therapeutics for inflammation and Alzheimer's disease. The main 187 targets will be glutaminyl cyclase (QC) and cyclin- dependent kinase 9 (CDK9). QC is a metalloenzyme involved in peptide hormone final maturation and inhibition of QC may provide a Glutaminyl-peptide cyclotransferase inhibitors Inflammation Preclinical PO Germany Probiodrug Originator Germany Pharmaceutical Private strategy in the treatment of Alzheimer's disease [CONT.] Probiodrug Owner Germany Pharmaceutical Private Research programme: tau protein TauRx Pharmaceuticals of Singapore is Tau protein inhibitors Alzheimer's disease Preclinical PO Singapore TauRx Pharmaceuticals Originator Singapore Pharmaceutical inhibitors - TauRx Pharmaceuticals undertaking a research programme to develop orally available, second-generation inhibitors of tau protein for the treatment of Alzheimer's 188 disease (AD). The programme is in preclinical development. TauRx is pursuing commercialisation, licensing TauRx Pharmaceuticals Owner Singapore Pharmaceutical and/or partnering opportunities for its programme in neurodegenerative disorders, particularly AD. [CONT.] Research programme: therapeutic HanAll Biopharma is a Korean-based company HL 152B AMP activated protein kinase stimulants Age-related macular degeneration Preclinical Ophthalmic South Korea HanAll Biopharma Originator South Korea Pharmaceutical Private agents - HanAll Biopharma that is developing therapeutic agents (oral HL 156Can Cell adhesion molecule inhibitors Autoimmune disorders Preclinical IV South Korea Korea Research Institute of Chemical Technology Originator South Korea Institution N/A biopharmaceuticals and/or small molecules) for HL004 Emt protein-tyrosine kinase inhibitors Cancer Preclinical PO South Korea treatment of major diseases of global HL010 Fc receptor antagonists Dry eyes Preclinical Ophthalmic South Korea importance, such as diabetes, obesity, HL011 Gluconeogenesis inhibitors Hypertension Preclinical PO South Korea, USA cardiovascular indications (hypertension, HL020 Immunomodulators Inflammatory bowel diseases Preclinical PO South Korea hyperlipidaemia, atherosclerosis, angina), HL021 Tumour necrosis factor alpha inhibitors Uveitis Preclinical Ophthalmic South Korea opthalmic disorders, autoimmune disorders, and HL022 Alzheimer's disease Research PO South Korea cancer. [CONT.] HL023 Angina pectoris Research PO South Korea HL024 Asthma Research Unknown route South Korea HL025 Atherosclerosis Research PO South Korea HL026 Atopic dermatitis Research Unknown route South Korea HL027 Diabetes mellitus Research PO South Korea HL030 Obesity Research PO South Korea HL034 (oral TPO agent) - HanAll Parkinson's disease Research PO South Korea 189 HL036 (anti-TNF-alpha protein) Thrombocytopenia Research PO South Korea HL038 HL039 HL051 HL076 HL102 HL130 HL152B HL156 HL156Can HL157 (oral monoclonal antibody) - HanAll Biopharma HL160 metformin butyrate - HanAll BioPharma Second-generation metformin products - HanAll Biopharma Research programme: tissue Warren Pharmaceuticals, is using its tissue Tissue protection technology research Alzheimer's disease Preclinical Unknown route USA Asterand plc Technology Provider USA Pharmaceutical Public protection technology - protection technology to develop haemopoietic programme - Warren Pharmaceuticals/Lundbeck Lundbeck/Warren Pharmaceuticals cytokines which cross the blood brain barrier, as potential therapeutics for the treatment of tissue injury associated with conditions such as brain 190 and spinal cord injuries, Alzheimer's Disease and other neurological disorders. H. Lundbeck A/S is collaborating with Warren in the development of Tissue-protective cytokines Neuroprotection Preclinical Unknown route USA Lundbeck A/S Collaborator World Large Pharma, Pharmaceutical Public therapeutics in these neurological and pyschiatric Warren Pharmaceuticals Originator USA Biotechnology Private areas [CONT.] Warren Pharmaceuticals Owner USA Biotechnology Private Research programme: umbilical cord Saneron CCEL Therapeutics is collaborating with hUCB stem cell therapies - Saneron CCEL Amyloid beta-protein inhibitors Alzheimer's disease Preclinical IV USA Cryo-Cell International Funder USA Technology provider Public blood stem cell therapies - Saneron the University of South Florida to develop human Therapeutics CCEL Therapeutics umbilical cord blood (hUCB) stem cell therapies based on the U-CORD-CELL™ technology 191 platform. The programme is focused on the early Human umbilical cord blood stem cell therapies - Cell replacements Amyotrophic lateral sclerosis Preclinical IV USA Saneron CCEL Therapeutics Originator USA Biotechnology Private intervention and treatment of several Saneron CCEL Therapeutics neurodegenerative, cardiovascular and metabolic U-CORD-CELL™ Enzyme stimulants Mucopolysaccharidosis III Preclinical IV USA Saneron CCEL Therapeutics Owner USA Biotechnology Private disorders that lack suitable treatment options. Nerve growth factor stimulants Myocardial infarction Preclinical IV USA University of Minnesota Technology Provider USA University N/A [CONT.] Stroke Preclinical IV USA University of South Florida Collaborator USA University N/A Research programme: vaccines - VLP VLP Biotech is focusing on developing a universal Allergy vaccine - VLP Biotech Immunomodulators Hepatitis C Preclinical Unknown route USA VLP Biotech Originator USA Biotechnology Private Biotech vaccine against influenza A virus strains, as well Alzheimer's disease vaccine - VLP Biotech Immunostimulants Influenza virus infections Preclinical Unknown route USA VLP Biotech Owner USA Biotechnology Private as vaccines against malaria, hepatitis C virus, Atherosclerosis vaccine - VLP Biotech Malaria Preclinical Unknown route USA cancer, lipid disorders (atherosclerosis and Cancer vaccine - VLP Biotech Alzheimer's disease Research Unknown route USA Atherosclerosis Research Unknown route USA 192 obesity), Alzheimer's disease and various Hepatitis C virus vaccine - VLP Biotech hypersensitivities. VLP Biotech's vaccine platform Hypersensitivity vaccine - VLP Biotech Cancer Research Unknown route USA is based on virus-like particles (VLP). [CONT.] Influenza A virus vaccine - VLP Biotech Hypersensitivity Research Unknown route USA Lipid disorder vaccine - VLP Biotech Lipid metabolism disorders Research Unknown route USA Malaria vaccine - VLP Biotech Obesity Research Unknown route USA Obesity vaccine - VLP Biotech Research programme: vaccines Idera Pharmaceuticals and Merck are Immunostimulants Cancer Preclinical Unknown route USA Idera Pharmaceuticals Collaborator USA Biotechnology Public containing toll-like receptor agonists collaborating on the development of vaccines - Idera/Merck containing agonists of toll-like receptors (TLRs) 7, 8 and 9 for the treatment and prevention of 193 cancer, infectious diseases and Alzheimer's disease. Preclinical development is underway for cancer, while early research activities are in Toll-like receptor 7 agonists Alzheimer's disease Research Unknown route USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public progress for infectious diseases and Alzheimer's Toll-like receptor 8 agonists Bacterial infections Research Unknown route USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public disease, in the US. [CONT.] Toll-like receptor 9 agonists Viral infections Research Unknown route USA RO 638695 Scientists at the University College of London are CPHPC Alzheimer's disease Preclinical Unknown route United Kingdom, USA Roche Originator Switzerland Large Pharma, Pharmaceutical Public collaborating with Roche in the development of RO 638695 for the treatment of Alzheimer's 194 disease. RO 638695 inhibits the binding of a blood protein called serum amyloid P (SAP) component to amyloid fibrils. The compound is currently undergoing preclinical trials. Roche Owner Switzerland Large Pharma, Pharmaceutical Public Etanercept liposomal - Neurokine Neurokine Pharmaceuticals in Canada is NK 002 Tumour necrosis factor inhibitors Alzheimer's disease Research Unknown route Canada Neurokine Pharmaceuticals Originator Canada Pharmaceutical Public Pharmaceuticals developing NK 002 (liposomal encapsulated etanercept) for the treatment of Alzheimer's 195 disease. The company expects to complete large scale preparation and optimization of liposomal etanercept and complete trials to assess blood brain barrier penetration by August 2011. NK-002 Neurokine Pharmaceuticals Owner Canada Pharmaceutical Public Research programme: Alzheimer's Bristol-Myers Squibb and Meso Scale Discovery Alzheimer's disease (Diagnosis) Research Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public disease diagnostic agents - Bristol- are collaborating in the development of Myers Squibb/Meso Scale Discovery diagnostic assays for Alzheimer's disease (AD). The diagnostic assays will be developed using 196 Meso Scale Discovery's MULTI-ARRAY® technology platform, and will measure cerebrospinal fluid biomarkers for use in AD research and drug development. [CONT.] Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

Research programme: Alzheimer's GE Healthcare in collaboration with Janssen Alzheimer's disease (Diagnosis) Research Unknown route USA GE Healthcare Originator United Kingdom Technology provider Public disease diagnostics - GE Pharmaceutica N.V. is developing non-invasive or Healthcare/Janssed Pharmaceutica minimally invasive diagnostic biosignatures for pre-symptomatic detection of Alzheimer's disease (AD). The collaboration will combine 197 Janssen's clinical, biomarker and informatics expertise with GE Healthcare's diagnostic capabilities to identify diagnostic biosignatures, also known as combination of biomarkers, that are specific to AD [CONT.] Janssen Pharmaceutica Originator Belgium Pharmaceutical Public Research programme: Alzheimer's Ichor Medical Systems and the Institute for Immunostimulants Alzheimer's disease Research IM USA Ichor Medical Systems Originator USA Technology provider Private disease DNA-vaccine - Ichor Medical Molecular Medicine, in the US, are developing an Systems intramuscular DNA-vaccine for the treatment of Alzheimer's disease. DNA vaccine encoding 198 proteins, which are implicated in the development Ichor Medical Systems Technology Provider USA Technology provider Private of Alzheimer's disease, will be delivered using Institute for Molecular Medicine Originator USA Institution N/A Ichor's proprietary TriGrid™ electroporation National Institute of Neurological Disorders and Stroke Funder USA Institution N/A technology. This vaccine is undergoing development in the US. [CONT.] University of California at Irvine Collaborator USA University N/A Research programme: Alzheimer's Cangene Corporation and the University of British Amyloid beta-protein inhibitors Alzheimer's disease Research Parenteral Canada Cangene Corporation Originator Canada Biopharmaceutical Public disease immunotherapy - Columbia (UBC) are developing immune-based Cangene/University of British therapies for the treatment of Alzheimer's 199 Columbia disease. Research led by an investigator at UBC succeeded in targeting a specific epitope of amyloid beta (Abeta) oligomers that is not Immunomodulators Cangene Corporation Owner Canada Biopharmaceutical Public present in regular Abeta molecules. [CONT.] University of British Columbia Technology Provider Canada University N/A Research programme: Alzheimer's ADispell is developing small molecule, Nicotinic receptor modulators Alzheimer's disease Research Unknown route USA ADispell Originator USA Biotechnology Private disease therapeutics - ADispell neuroprotective drug candidates that target a novel site on the nicotinic acetylcholine receptor (nAChR) for the treatment of Alzheimer's 200 disease. The company licensed a proprietary technology from Cornell University that acts on brain neurons to treat and prevent cognition loss caused by Alzheimer's disease and other ADispell Owner USA Biotechnology Private cognition disorders. [CONT.] Cornell University Technology Provider USA University N/A Research programme: Alzheimer's Astellas Pharma and RIKEN are collaborating on Undefined mechanism Alzheimer's disease Research Unknown route Japan Astellas Pharma Originator Japan Large Pharma, Pharmaceutical Public disease therapeutics - Astellas the discovery and development of therapies for Pharma/RIKEN Alzheimer's disease. The companies will first identify candidate molecular targets for drug therapy by analysis of animal models of 201 Alzheimer's disease and samples from patients with the disease. The involvement of such candidate targets in the pathogenic mechanism of Alzheimer's disease will then be evaluated, and their potential as targets for drug discovery will be validated [CONT.] RIKEN Originator Japan Institution N/A Research programme: Alzheimer's AstraZeneca and the University of Pennsylvania Alzheimer's disease Research Unknown route USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public disease therapeutics - AstraZeneca School of Medicine are collaborating on the development of novel therapeutics for the 202 potential treatment of Alzheimer's disease (AD). The research will focus on the tau-mediated neurodegeneration in AD. Early research is underway in the US. Penn State College of Medicine Originator USA University N/A Research programme: Alzheimer's AstraZeneca and academic research laboratories, Apolipoprotein E modulators Alzheimer's disease Research Unknown route USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public disease therapeutics - led by Weill Cornell Medical College, are AstraZeneca/Weill Cornell Medical collaborating to assess the role of the College apolipoprotein E4 genotype (ApoE) in the 203 The Feinstein Institute for Medical Research Collaborator USA Institution N/A development of Alzheimer's disease and to University of British Columbia Collaborator Canada University N/A discover therapeutics against this target. Washington University School of Medicine Collaborator USA University N/A Development is at the research stage in the US. Weill Cornell Medical College Originator USA University N/A Research programme: Alzheimer's Axerion Therapeutics and MedImmune, the global Alzheimer's disease Research Unknown route USA Axerion Therapeutics Licensee USA Biotechnology Private disease therapeutics - Axerion biologics arm of AstraZeneca, are collaborating Therapeutics/ MedImmune to develop small and large molecules for the treatment of Alzheimer's disease. Development is at the research stage in the US. 204 Both companies will work together to develop MedImmune Sub-licensee USA Biotechnology Public compounds that directly block the amyloid-beta (Abeta) oligomer binding to cellular prion proteins in the brain. [CONT.] Yale University Originator USA University N/A Yale University Owner USA University N/A Research programme: Alzheimer's Axxam in Italy and a US-based public charity, Purinoceptor P2Z antagonists Alzheimer's disease Research Unknown route Italy Alzheimers Drug Discovery Foundation Collaborator USA Company disease therapeutics - the Alzheimer's Drug Discovery Foundation, are Axxam/Alzheimer's Drug Discovery collaborating on the development of small Foundation molecule compounds that block the purinergic receptor P2Z (also known as P2X7) as potential 205 therapies for Alzheimer's disease. Axxam is to conduct the drug discovery and development and ADDF is contributing financially to the programme. Development is at the research Axxam Originator Italy Biotechnology stage in Italy. [CONT.] Axxam Owner Italy Biotechnology Research programme: Alzheimer's MIVAC Development in Sweden is developing Amyloid beta-protein modulators Alzheimer's disease Research Parenteral Sweden MIVAC Development Originator Sweden Biopharmaceutical Private disease therapeutics - MIVAC monoclonal antibodies for the potential treatment Development of Alzheimer's disease. The company's research is based around its discovery of methods to engineer preparations of stabilised, highly-toxic 206 oligomeric amyloid-beta (Abeta). Soluble oligomeric aggregates of the Abeta peptide are thought to be involved in the pathogenesis of Alzheimer's disease. [CONT.] MIVAC Development Owner Sweden Biopharmaceutical Private Research programme: Alzheimer's Oligomerix is developing small molecules and Tau protein inhibitors Alzheimer's disease Research Unknown route USA OLIGOMERIX Originator USA Biopharmaceutical Private disease therapeutics - Oligomerix antibodies that target soluble aggregates of tau protein as a disease-modifying treatment option 207 for Alzheimer's disease (AD). Development is focussed on compounds that inhibit tau oligomer formation, disrupt tau oligomers or inhibit tau- mediated neurotoxicity. [CONT.] OLIGOMERIX Owner USA Biopharmaceutical Private Research programme: Alzheimer's Pharnext, Biosystems International, the Undefined mechanism Alzheimer's disease Research Unknown route France BioSystems International Originator France Company disease therapeutics - University of Bordeaux Segalen and Inserm are Pharnext/Biosystems collaborating on a 6-year project to develop therapeutics and diagnostics for Alzheimer's 208 disease. The project, known as DIPPAL, will be lead by Pharnext and will involve development of Pleodrugs™; cocktails of low-dose, off-patent INSERM Originator France Institution N/A drugs which have been approved for other diseases. [CONT.] Research programme: Alzheimer's Pharnext, Biosystems International, the Undefined mechanism disease therapeutics - University of Bordeaux Segalen and Inserm are Pharnext/Biosystems collaborating on a 6-year project to develop therapeutics and diagnostics for Alzheimer's 208 disease. The project, known as DIPPAL, will be lead by Pharnext and will involve development of Pleodrugs™; cocktails of low-dose, off-patent drugs which have been approved for other Pharnext Originator France Biopharmaceutical diseases. [CONT.] University of Bordeaux Originator France University N/A Research programme: Alzheimer's Reviva Pharmaceuticals in the US is developing RP4000 - Reviva Pharmaceuticals Undefined mechanism Alzheimer's disease Research PO USA Reviva Pharmaceuticals Originator USA Pharmaceutical Private disease therapeutics - Reviva orally bioavailable therapeutics for the treatment Pharmaceuticals of Alzheimer's disease. The company's internally discovered small molecule therapeutics are 209 designed to be safe, highly potent and selective for improved patient compliance. Designated RP 4000, Reviva's programme targeting Alzheimer's disease is at the research stage of development. [CONT.] Reviva Pharmaceuticals Owner USA Pharmaceutical Private Research programme: Alzheimer's Umecrine Cognition is developing compounds for GABA A receptor modulators Alzheimer's disease Research Unknown route Sweden Umecrine Cognition Originator Sweden Pharmaceutical Private disease therapeutics - Umecrine the treatment of Alzheimer's disease and Cognition dementia. These compounds selectively modulate 210 the effects of GABA-steroids on GABA A receptors in the brain. A research programme to investigate these compounds is underway in Umecrine Cognition Owner Sweden Pharmaceutical Private Sweden. [CONT.] Research programme: Alzheimer's Yuma Therapeutics is developing small molecule Tau protein inhibitors Alzheimer's disease Research Unknown route USA Yuma Therapeutics Originator USA Biopharmaceutical Private disease therapeutics - Yuma compounds targeting tau pathway for the Therapeutics treatment of Alzheimer's disease (AD). One of the hallmarks of AD is the presence of neurofibrillary tangles in the brains of affected 211 individuals. These tangles are made up of aberrant tau protein clusters comprising paired helical filaments (PHFs, as characterised by a double-twisted ribbon shape), which aggregate over time causing toxicity and neuronal cell death Yuma Therapeutics Owner USA Biopharmaceutical Private Research programme: Alzheimer's Icogenex[CONT.] (formerly Icogen) Corporation is EPalpha Amyloid beta-protein precursor modulators Alzheimer's disease Research Unknown route USA Icogenex Corporation Originator USA Pharmaceutical Private disease therapies - Icogenex developing therapeutics for the treatment of Alzheimer's disease (AD). The company are using its ICOCEPT™ platform to investigate 212 inappropriate proteolytic processing and to develop small molecules with the aim of normalising the beta-amyloid production without disrupting other systems. Preclinical development is ongoing in the USA for the treatment of AD. EPbeta Icogenex Corporation Owner USA Pharmaceutical Private Research programme: Alzheimer's Shionogi[CONT.] and Kyoto University are collaborating SK Project Central nervous system modulators Alzheimer's disease Research Unknown route Japan Kyoto University Originator Japan University N/A disease therapies - Kyoto on a drug discovery and medical research University/Shionogi project, the SK Project, to develop therapies for Alzheimer's disease and other disorders of the 213 central nervous system. The project is based on identifying new drug targets relating to synapses and the regeneration of neurological function. Development is at the stage of early research in Japan. [CONT.] Shionogi Originator Japan Large Pharma, Pharmaceutical Public Research programme: Alzheimer's Alectos Therapeutics in collaboration with Merck Hexosaminidase C modulators Alzheimer's disease Research PO Canada, USA Alectos Therapeutics Originator Canada Biopharmaceutical Private disease therapy - Alectos/Merck is developing small molecule therapeutics for the treatment of Alzheimer's disease. The collaboration is based on Alectos' proprietary 214 portfolio of compounds, modulators of O-linked N- acetylglucosaminidase (O-GlcNAcase), an enzyme implicated in the development of Alzheimer's disease. Development is at the research stage in the US and Canada. Merck & Co Originator USA Large Pharma, Pharmaceutical Public Research programme: amyloid beta- AstraZeneca is developing therapeutics that ADDL inhibitors Amyloid beta-protein inhibitors Alzheimer's disease Research Unknown route Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public derived diffusible ligand inhibitors - target soluble polymers (SPs) of the amyloid AstraZeneca beta peptide, also known as amyloid beta- derived diffusible ligands (ADDLs), for the potential treatment of Alzheimer's disease. 215 ADDLs are highly ordered aggregates of amyloid beta1-42 peptides which are believed to provoke deposition of hyperphosphorylated Tau (paired helical filaments or PHF-Tau). [CONT.] AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

Research programme: amyloid Critical Outcome Technologie (COTI) is Amyloid precursor protein secretase inhibitors Alzheimer's disease Research PO Canada Critical Outcome Technologies Originator Canada Biotechnology Private precursor protein secretase developing oral, small molecule inhibitors that inhibitors - Critical Outcome target amyloid precursor protein secretases (beta- Technologies secretase and gamma-secretase) for the 216 treatment of Alzheimer's disease (AD). Using its computational platform technology, CHEMSAS®, COTI has optimised six lead candidates on three different scaffolds that are ready for synthesis and preclinical evaluation. [CONT.] Critical Outcome Technologies Owner Canada Biotechnology Private Research programme: amyloid Elan Pharmaceuticals, a subsidiary of Elan ELND007 Amyloid precursor protein secretase inhibitors Alzheimer's disease Research Unknown route USA Elan Pharmaceuticals Originator USA Biotechnology Public precursor protein secretase Corporation, is developing small molecule inhibitors - Elan inhibitors of amyloid precursor protein secretase (beta-secretase and gamma-secretase) for the 217 treatment of Alzheimer's disease (AD). Neurodegeneration in AD is thought to result from the pathological cascade initiated by formation of insoluble plaques of accumulated Elan Pharmaceuticals Owner USA Biotechnology Public beta-amyloid (Abeta) peptides. [CONT.] PPD Collaborator World CRO Public Research programme: analgesics and Biogen Idec and the Johns Hopkins Brain Science BSi-Biogen Idec Research Program Undefined mechanism Alzheimer's disease Research Unknown route USA Biogen Idec Originator USA Large Pharma, Biotechnology Public neurodegenerative disorders Institute (BSi) are collaborating to discover and therapies - Biogen Idec/BSi develop therapies for pain and for 218 neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease (and possibly Multiple sclerosis Research Unknown route USA Johns Hopkins Brain Science Institute Originator USA Institution N/A also Parkinson's disease). Development is at the Neurodegenerative disorders Research Unknown route USA early research stage in the US. Pain Research Unknown route USA Research programme: BACE1 protein Medivir AB is undertaking a research programme Alzheimer's disease protease inhibitors - Medivir BACE1 protein inhibitors Alzheimer's disease Research Unknown route Sweden Medivir AB Originator Sweden Pharmaceutical Public inhibitors - Medivir AB to develop multiple series of compounds as AB inhibitors of BACE1 (beta-site amyloid precursor protein-cleaving enzyme) for the treatment of Alzheimer's disease (AD). Lead compounds are 219 undergoing optimisation in preparation for advanced preclinical development in Sweden.

BACE1 catalyses the first step of the two-step Medivir AB Owner Sweden Pharmaceutical Public amyloid precursor protein (APP) cleavage process in the brain, i [CONT.] Research programme: catalytic Ozgene is developing catalytic antibodies for the CATAB I - Ozgene Undefined mechanism Alzheimer's disease Research Parenteral Australia Ozgene Originator Australia Company antibody therapeutics - Ozgene treatment of various diseases, including rheumatoid arthritis, HIV infections and Alzheimer's disease. Catalytic antibodies are 220 highly substrate specific and catalyse a number of biological processes including the CATAB II - Ozgene HIV infections Research Parenteral Australia Ozgene Owner Australia Company actication/inactivation of proteins. Ozgene has CATAB III - Ozgene Rheumatoid arthritis Research Parenteral Australia patented a catalytic antibody platform and early CATAB IV - Ozgene research is ongoing in Australia. [CONT.] CATAB V - Ozgene Research programme: CNS disorders Spencer Pharmaceutical and National Undefined mechanism Alzheimer's disease Research PO USA National Pharmaceutical Corp Originator USA therapeutics - National Pharmaceutical are collaborating to develop Pharmaceutical/Spencer orally available prodrugs to treat central nervous Pharmaceutical system (CNS) disorders, with particular focus on Alzheimer's and Parkinson's disease. Using 221 Spencer's drug delivery technology as the primary platform, the companies will work on bio- oxidable prodrugs that can efficiently cross the blood brain barrier, where they are converted to the parent drug in the CNS via a redox-activation process [CONT.] Parkinson's disease Research PO USA Spencer Pharmaceutical Originator USA Biopharmaceutical Private Research programme: G-protein Galapagos NV is undertaking a research GPR3 inhibitors programme Amyloid beta-protein precursor inhibitors Alzheimer's disease Research Unknown route Belgium Galapagos NV Originator Belgium Pharmaceutical Public coupled receptor 3 antagonists - programme focussed on the development of Galapagos small molecule drugs that target and inhibit the orphan G-protein coupled receptor 3 (GPR3) for 222 the treatment of Alzheimer's disease (AD). GPR3 was identified in human cells using Galapagos' technology platform. Development is at the early research stage in the Belgium. [CONT.] G protein-coupled receptor antagonists Galapagos NV Owner Belgium Pharmaceutical Public Research programme: Aquapharm Biodiscovery and the University of Hexosaminidase C inhibitors Alzheimer's disease Research Unknown route United Kingdom Aquapharm Biodiscovery Originator United Kingdom Biotechnology Private hexosaminidase-C-inhibitors - Dundee are developing hexosaminidase-C Aquapharm Biodiscovery/University inhibitors (O-GlcNAcase inhibitors) for the of Dundee treatment of Alzheimer's disease. Hexosaminidase-C modulates the solubility of the 223 proteins in the aggregates associated with the progressive neurodegeneration of Alzheimer's disease. The compounds being investigated are derived from Aquapharm's marine microbial University of Dundee Originator United Kingdom University N/A collection [CONT.] Research programme: memantine NeuroMolecular Pharmaceuticals is undertaking a Memantine analogues - NeuroMolecular Nitric oxide modulators Alzheimer's disease Research Unknown route USA NeuroMolecular Pharmaceuticals Originator USA Pharmaceutical Private derivatives - NeuroMolecular research programme to develop a series of Pharmaceuticals memantine derivatives with enhanced efficacy and improved tolerability for the treatment of 224 neurodegenerative disorders such as Alzheimer's disease (AD) and neuropathic pain. Development is at the early research stage in the US. [CONT.] NMDA receptor antagonists Neurodegenerative disorders Research Unknown route USA NeuroMolecular Pharmaceuticals Owner USA Pharmaceutical Private Neuropathic pain Research Unknown route USA Research programme: Biogen Idec and Neurimmune Therapeutics are Alpha-synuclein inhibitors Alzheimer's disease Research Parenteral Switzerland, USA Biogen Idec Licensee World Large Pharma, Biotechnology Public neurodegenerative disease collaboratively developing fully human antibodies therapeutics - Biogen for the treatment of neurodegenerative diseases. Idec/Neurimmune Therapeutics The alliance will focus on the development of antibodies that bind to amyloid beta (Abeta), alpha-synuclein, tau, and TDP-43. These targets 225 may result in antibodies for the treatment and prevention of a wide variety of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral Amyloid beta-protein inhibitors Neurodegenerative disorders Research Parenteral Switzerland, USA Neurimmune Therapeutics Originator Switzerland Biotechnology Private sclerosis (ALS). [CONT.] Tau protein inhibitors Neurimmune Therapeutics Owner Switzerland Biotechnology Private TDP-43 protein inhibitors Research programme: Aurogen is developing therapeutics for the Insulin-like growth factor I stimulants Alzheimer's disease Research Parenteral USA Aurogen Originator USA Biotechnology Private neurodegenerative disorders treatment of neurodegenerative diseases, therapeutics - Aurogen including diabetic neuropathy and Alzheimer's disease. Development is at the early research 226 stage in the US. The company's proprietary technology is based Diabetic neuropathies Research Parenteral USA Aurogen Owner USA Biotechnology Private on the discovery of the neurotrophic role of insulin-like growth factors (IGF) that are able to cross the blood-brain-barrier and prevent the death of neurons. [CONT.] Research programme: Prothena Corporation (originally Elan Protein aggregation modulators Alzheimer's disease Research Unknown route United Kingdom Prothena Corporation Originator Ireland Pharmaceutical Public neurodegenerative therapeutics - Corporation) and The University of Cambridge Prothena Corporation/The University are collaborating to develop treatments for of Cambridge Alzheimer's disease and Parkinson's disease. The goal of the collaboration is to discover novel 227 compounds that can alter the molecular behaviour of proteins (i.e folding, misfolding, aggregation and turnover) associated with these Protein conformation modulators Parkinson's disease Research Unknown route United Kingdom University of Cambridge Originator United Kingdom University N/A neurodegenerative disorders. [CONT.] Protein folding modulators Research programme: Afraxis is developing inhibitors of p21-activated P21 activated kinase inhibitors Alzheimer's disease Research Unknown route USA Afraxis Originator USA Biotechnology Private neuropsychotherapeutics - Afraxis kinase (PAK) as potential therapeutics for CNS disorders such as Alzheimer's disease and mental disorders such as schizophrenia. The company has stated that the PAK inhibitors function as 228 disease-modifying agents that directly target the cellular pathology underlying the disorders. PAK is a protein kinase that regulates the development and activity of dendritic spines CNS disorders Research Unknown route USA Afraxis Owner USA Biotechnology Private [CONT.] Schizophrenia Research Unknown route USA Genentech Licensee World Large Pharma, Biotechnology Public Research programme: p75 ligands - PharmatrophiX in the US is developing small Amyloid beta-protein inhibitors Alzheimer's disease Research Unknown route USA PharmatrophiX Originator USA Biotechnology Private PharmatrophiX molecule p75 ligands for the treatment of Alzheimer's disease and possibly other neurological disorders such as Parkinson's disease and multiple sclerosis. The compounds imitate the function of neurotrophins, interacting 229 with neurons susceptible to degeneration in Alzheimer's disease. Specifically, they have the potential to provide protection against degeneration caused by the beta-amyloid protein, a possible cause of Alzheimer's disease. [CONT.] PharmatrophiX Owner USA Biotechnology Private Research programme: protein folding Reata Pharmaceuticals is developing small Protein folding modulators - Reata Alpha-synuclein inhibitors Alzheimer's disease Research PO USA Reata Pharmaceuticals Originator USA Biopharmaceutical Private modulators - Reata Pharmaceuticals molecule, protein folding modulators for the Pharmaceuticals treatment of various genetic diseases caused by misfolded proteins. Defects in protein folding Protein misfolding reagents for Amyloid beta-protein inhibitors Amyotrophic lateral sclerosis Research PO USA Reata Pharmaceuticals Owner USA Biopharmaceutical Private 230 underlie a large number of diseases including neurodegenerative diseases - Reata cancer, amyotrophic lateral sclerosis (ALS), Pharmaceuticals Alzheimer's disease (AD), Parkinson's disease RTA 801 Protein folding modulators Huntington's disease Research PO USA (PD), cystic fibrosis, and Huntington's disease SOD1 reactivators - Reata Pharmaceuticals Superoxide dismutase stimulants Parkinson's disease Research PO USA (HD). [CONT.] SOD1 stabilisers - Reata Pharmaceuticals Research programme: schizophrenia Orion Pharma in Finland is researching ORM-14540 Alpha 2c adrenergic receptor antagonists Alzheimer's disease Research Unknown route Finland Orion Originator Finland Pharmaceutical Public and Alzheimer's disease therapeutics compounds for the potential treatment of - Orion Pharma schizophrenia and Alzheimer's disease. Three lead compounds emerged from this programme, ORM 14540, ORM 10921, and ORM 12741 [see 231 separate profile]. ORM 14540 completed phase 0 development in an IV formulation in healthy men (NCT00831077), with potential for schizophrenia and possibly also Alzheimer's disease. [CONT.] Undefined mechanism Schizophrenia Research IV Finland Orion Owner Finland Pharmaceutical Public Research programme: subtype- Mnemosyne Pharmaceuticals is developing small NMDA receptor modulators Alzheimer's disease Research Unknown route USA Jubilant Pharmaceuticals Collaborator USA Pharmaceutical selective NMDA receptor modulators - molecule therapeutics that target and modulate Mnemosyne Pharmaceuticals the specific NMDA receptor subtypes of the receptor subunit, NR2, as potential treatment for cognitive and neuropsychiatric disorders. 232 Development is at the research stage and indications being investigated include schizophrenia (the lead indication), Alzheimer's disease (AD), recovery from stroke and traumatic brain injury, and attention-deficit hyperactivity disorder (ADHD) [CONT.] Research programme: subtype- Mnemosyne Pharmaceuticals is developing small selective NMDA receptor modulators - molecule therapeutics that target and modulate Mnemosyne Pharmaceuticals the specific NMDA receptor subtypes of the receptor subunit, NR2, as potential treatment for cognitive and neuropsychiatric disorders. 232 Development is at the research stage and indications being investigated include NR2B N-Methyl D-Aspartate receptor modulators Attention-deficit hyperactivity disorder Research Unknown route USA Mnemosyne Pharmaceuticals Originator USA Biotechnology Private schizophrenia (the lead indication), Alzheimer's disease (AD), recovery from stroke and Brain injuries Research Unknown route USA Mnemosyne Pharmaceuticals Owner USA Biotechnology Private traumatic brain injury, and attention-deficit Schizophrenia Research Unknown route USA hyperactivity disorder (ADHD) [CONT.] Stroke Research Unknown route USA Research programme: sustained- Daewoong Pharmaceutical is developing IMD2 (SR form) Undefined mechanism Alzheimer's disease Research Unknown route South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public release drugs - Daewoong sustained-release incrementally modified drugs Pharmaceutical (IMDs) for the treatment of thrombosis (IMD2), 233 Alzheimer's disease (IMD3), and gastric ulcers (IMD4). The drugs are at the research stage of IMD3 (SR form) Gastric ulcer Research Unknown route South Korea Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public development in South Korea. IMD4 (SR form) Thrombosis Research Unknown route South Korea Research programme: Tau Bristol-Myers Squib and the Gladstone Institutes Tau protein modulators Alzheimer's disease Research Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public dysfunction regulators - Bristol- are conducting a discovery-based research Myers Squib/Gladstone Institutes collaboration to identify and validate targets that affect Tau dysfunction for the treatment of 234 Alzheimer's disease. Tau is a protein that binds the internal skeleton of the cell and may help regulate brain cell activity. Tau forms abnormal deposits, termed neurofibrillary tangles, in Alzheimer's disease. [CONT.] The J. David Gladstone Institutes Originator USA Institution N/A Research programme: tau protein BIOALVO, located in Portugal, has a research BLV0703 Tau protein modulators Alzheimer's disease Research Unknown route Portugal BIOALVO Originator Portugal Biopharmaceutical Private modulators - BIOALVO programme directed at tauopathies for the treatment of neurodegenerative diseases such as Alzheimer's disease and Frontotemporal Dementia (FTD) with Parkinsonism. Tau protein 235 interacts with tubulin to stabilise microtubules and promote tubulin assembly into microtubules. Tau aggregation into neurofibrillary tangles (NFT) BLV200703 Neurodegenerative disorders Research Unknown route Portugal BIOALVO Owner Portugal Biopharmaceutical Private is a major feature in some neurodegenerative SDGI-T200801 Parkinson's disease Research Unknown route Portugal diseases [CONT.] TAU Programme Research progranne: anti-beta- sanofi-aventis is developing a monoclonal Amyloid beta-protein inhibitors Alzheimer's disease Research Parenteral France Rockefeller University Originator USA University N/A amyloid antibodies - sanofi- antibody, targeting specific forms of the amyloid aventis/Rockefeller University beta (Abeta) parenchymal plaque for the 236 treatment of Alzheimer's disease. sanofi-aventis licensed a specific antibody from the Rockefeller University to be studied. Preclinical research is Rockefeller University Owner USA University N/A being conducted in France. Sanofi Licensee World Large Pharma, Pharmaceutical Public VBY 129 Virobay is developing VBY 129, a selective, orally Cathepsin S inhibitors Alzheimer's disease Research PO USA Unknown Originator USA Company active, small-molecule cathepsin S inhibitor, for the treatment of Alzheimer's disease. The drug was in-licensed by Virobay from an undisclosed company and appears to be suitable for once- 237 daily dosing. Development is at the stage of early research in the US. VBY 129 was originally being developed to treat Psoriasis Discontinued(I) PO USA Unknown Owner USA Company autoimmune disease. [CONT.] Virobay Licensee USA Pharmaceutical Private