Alzheimer's Disease (Phase I - II) - Springerstatic.springer.com/sgw/documents/1431373/application/pdf/Alzheimer... · BAN-2401 Alzheimer's disease (Early-stage disease) Phase II

Indication Phase Route Country Name Role Country Type OwnershipOctapharma has developed an intravenously

administered human normal immunoglobulin

(10% concentration) for use in disorders of the

immune system. The product was launched in

Europe in 2008 under the brand name octagam®

10% for several indications.

10% high purity immunoglobulin Immunodeficiency disorders Marketed IV Europe Octapharma Originator Switzerland Company

Octagam® 10% has been launched as

replacement therapy for primary

immunodeficiency syndromes such as: primary

humoral immunodeficiency (PI); [CONT.]

10% IVIG Immunodeficiency disorders Phase III IV USA Octapharma Owner Switzerland Company

NewGam Alzheimer's disease (In the elderly) Phase II IV USA

NewGam™

octagam 10%

octagam immunoglobulin 10%

octagam® 10%

octagam® 10%

EVP-6124 Cognition disorders Phase III PO USA Bayer HealthCare Originator Germany Pharmaceutical Public

MT-4666 Alzheimer's disease Phase II PO Japan, Romania, Russia, Serbia, Ukraine, USA Bayer HealthCare Owner Germany Pharmaceutical Public

Cognition disorders Phase II PO Russia, Serbia, Ukraine EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private

Mitsubishi Tanabe Pharma Corporation Licensee Asia Large Pharma, Pharmaceutical Public

AL 108 Microtubule-associated protein modulators Progressive supranuclear palsy II/III Intranasal Australia, Canada, France, Germany, United Kingdom, USA

(Fast Track)

Allon Therapeutics Licensee Canada Biotechnology Public

AL-108 Tau protein inhibitors Alzheimer's disease Phase II Intranasal USA National Institutes of Health (USA) Originator USA Institution N/A

AL108 Tubulin polymerisation promoters Mild cognitive impairment Phase II Intranasal USA Tel Aviv University Originator Israel University N/A

NAP Schizophrenia Phase II Intranasal USA

NAPVSIPQ Parkinson's disease Preclinical Intranasal USA

Alzheimer's disease Phase II PO Bulgaria, Canada, Czech Republic, France, Germany,

Greece, Poland, Russia, Slovakia, South Africa, Ukraine,

United Kingdom, USA

Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

Cognition disorders Phase II PO USA AbbVie Owner USA Biopharmaceutical Public

Alzheimer's disease (Combination therapy) Phase I PO USA

Alzheimer's disease (In the elderly, In volunteers) Phase I PO USA

Alzheimer's disease Phase II PO Russia, Ukraine Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

Schizophrenia Phase II PO USA AbbVie Owner USA Biopharmaceutical Public

Alzheimer's disease Phase II PO Russia, South Africa, Ukraine, United Kingdom Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

Neurological disorders (In volunteers) Phase I Unknown route USA AbbVie Owner USA Biopharmaceutical Public

Alzheimer's disease Phase II PO Switzerland AC Immune Originator Switzerland Biotechnology Private

AC Immune Owner Switzerland Biotechnology Private

AD 02 Amyloid beta-protein inhibitors Alzheimer's disease Phase II SC Austria, Croatia, Czech Republic, France, Germany, Slovakia AFFiRiS Originator Austria Biotechnology Private

AD 2 Immunostimulants AFFiRiS Owner Austria Biotechnology Private

AD02 GlaxoSmithKline Biologicals Licensee World Biotechnology Public

Alzheimer AD02

Alzheimer's disease Phase II Unknown route USA Avineuro Pharmaceuticals Licensee World Pharmaceutical Private

Anxiety disorders Phase II Unknown route USA ChemDiv Originator USA CRO Private

ChemDiv Owner USA CRO Private

Alzheimer's disease Phase II Unknown route USA Avineuro Pharmaceuticals Originator USA Pharmaceutical Private

Anxiety disorders Phase II Unknown route USA Avineuro Pharmaceuticals Owner USA Pharmaceutical Private

AZD1446 Alzheimer's disease Phase II PO Czech Republic, Hungary, Russia, Slovakia, Ukraine AstraZeneca Licensee World Large Pharma, Pharmaceutical Public

TC 6683 Alzheimer's disease (In volunteers) Phase I PO Japan Targacept Originator USA Biopharmaceutical Public

TC-6683 Alzheimer's disease (In volunteers:Trials completed) Phase I PO Sweden Targacept Owner USA Biopharmaceutical Public

Attention-deficit hyperactivity disorder Discontinued(II) PO USA

Alzheimer's disease Phase II PO USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

Mild cognitive impairment Phase II PO USA AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

Alzheimer's disease (In volunteers) Phase I PO Japan, Sweden, USA

Attention-deficit hyperactivity disorder (In volunteers) No development reported(I) PO Japan, Sweden, USA

12

AZD 5213 AstraZeneca is developing the small molecule

compound AZD 5213, a histamine H3 receptor

antagonist, for the treatment of Alzheimer's

disease and Gilles de la Tourette's syndrome.

Histamine H3 receptors control histamine

synthesis and release in the central nervous

system, while inhibiting the release of other

neurotransmitters including dopamine, serotonin

and norepinephrine. [CONT.]

AZD5213 Histamine H3 receptor antagonists

10

AVN 397 Avineuro Pharmaceuticals (US) is developing AVN

397, a small molecule, for the treatment of

anxiety and Alzheimer's disease. This agent

entered phase II development in June 2009.

AVN-397 Undefined mechanism

11

AZD 1446 AZD 1446 is a small molecule, alpha4beta2

nicotinic receptor agonist being developed by

AstraZeneca for the treatment of Alzheimer's

disease. Phase II development is underway in

this indication. Phase II development of AZD

1446 for the treatment of attention-deficit

hyperactivity disorder (ADHD) was discontinued.

[CONT.]

Alpha4 beta2 nicotinic receptor agonists

9

AVN 101 Avineuro Pharmaceuticals is developing AVN 101,

a small-molecule, serotonin 5-HT6 receptor

antagonist, for use as a cognitive enhancer in

patients with Alzheimer's disease (AD) and in the

treatment of anxiety. The compound was

originally discovered by the contract research

organisation, ChemDiv, and was subsequently

licensed to Avineuro. Phase II development of

AVN 101 is underway in the US.

AVN-101 Serotonin 6 receptor antagonists

7

ACI 91 AC Immune is developing an oral formulation of

small molecule ACI 91 for the treatment of

Alzheimer's disease in Switzerland. The

compound, developed using the company's

Morphomer™ technology platform, has the

potential to prevent or slow down Alzheimer's

disease by a dual mechanism of neuroprotection

and plaque reduction correlated with an inhibition

of beta-secretase, an amyloid precursor protein

secretase [CONT.]

ACI-91 BACE1 protein inhibitors

8

Affitope AD02 AFFiRiS GmbH and GlaxoSmithKline Biologicals

are developing affitope AD 02, a subunit vaccine

targeting amyloid-beta (Abeta) protein, for the

treatment of Alzheimer's disease (AD). The

antigenic component of the vaccine uses the N-

terminal end of Abeta and was developed using

AFFiRiS' affitope technology platform

(Affitome®). [CONT.]

5

ABT 288 AbbVie (formerly Abbott Laboratories) is

developing ABT 288 as a potential treatment for

Alzheimer's disease and schizophrenia. A phase II

trial in the treatment of Alzheimer's disease has

been completed in Russia and the Ukraine, and a

phase II trial in the treatment of schizophrenia

has been conducted in the US. [CONT.]

ABT-288 Neurotransmitter receptor modulators

6

ABT 384 AbbVie (formerly Abbott Laboratories) is

developing ABT 384 as a potential therapy for

the treatment of neurological disorders. A phase

II trial in patients with mild-to-moderate

Alzheimer's disease has been completed in

Russia, South Africa, Ukraine and the UK. It

appears that this therapy is being developed for

oral administration. [CONT.]

ABT-384 Undefined mechanism

4

ABT 126 AbbVie is developing ABT 126, an alpha 7

neuronal nicotinic receptor (alpha7 NNR)

antagonist, as an orally administered treatment

for Alzheimer's disease and cognition disorders in

patients with schizophrenia. Phase II

development for Alzheimer's disease is underway

in the US, Canada, South Africa and certain

European countries. Phase II development is

underway in the US for cognition disorders in

patients with schizophrenia. [CONT.]

ABT-126 Nicotinic receptor antagonists

2

EVP 6124 EnVivo Pharmaceuticals is developing the orally

administered, selective alpha-7 nicotinic

acetylcholine receptor (alpha7-nAChR) agonist,

EVP 6124, for the treatment of Alzheimer's

disease and cognition disorders. Improved

cholinergic function is known to reduce cognitive

deficits in patients with Alzheimer's disease, and

a selective alpha7-nAChR agonist may enhance

cognition without causing the adverse events

associated with overactivation of other nAChRs or

muscarinic acetylcholine receptors [CONT.]

Alpha7 nicotinic acetylcholine receptor agonists

3

Davunetide intranasal Davunetide is an eight-amino acid peptide (i.e.

Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from an

endogenous brain neuroprotective protein, called

activity-dependent neuroprotective protein

(ADNP). Allon Therapeutics (a subsidiary of

Paladin Labs) is developing an intranasal

formulation of davunetide (AL 108) for the

treatment of mild cognitive impairment (MCI)

related to schizophrenia, Alzheimer's disease

(AD), Parkinson's disease (PD) and progressive

supranuclear palsy (PSP; a type of

frontotemporal dementia) [CONT.]

Drug Development Phase Organisations

1

Immune globulin 10% -

Octapharma

Immunostimulants

Alzheimer's Disease (Phase I - II)

Drug Introduction Synonyms Mechanism Of Action

BAN-2401 Alzheimer's disease (Early-stage disease) Phase II Parenteral United Kingdom, USA BioArctic Neuroscience Originator Sweden Biotechnology Private

BAN2401 BioArctic Neuroscience Owner Sweden Biotechnology Private

Eisai Co Ltd Licensee World Large Pharma, Pharmaceutical Public

AAB-001 Amyloid beta-protein inhibitors Alzheimer's disease Phase II SC USA Elan Corporation Originator Ireland Large Pharma, Biotechnology Public

AAB-001 SubQ Immunosuppressants Alzheimer's disease Discontinued(III) IV Australia, Canada, Europe, Japan, Mexico, South Africa,

South America, USA (Fast Track)

JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical

MedImmune Technology Provider USA Biotechnology Public

Pfizer Owner USA Large Pharma, Pharmaceutical Public

Wyeth Originator USA Large Pharma, Pharmaceutical Public

Alzheimer's disease vaccine (CAD106) -

Cytos/Novartis

Amyloid beta-protein inhibitors Alzheimer's disease Phase II IM Canada, European Union, Norway, Switzerland, USA Cytos Biotechnology Originator Switzerland Biotechnology Public

CAD106 Immunomodulators Alzheimer's disease Phase II SC European Union, Switzerland, USA Cytos Biotechnology Owner Switzerland Biotechnology Public

Immunodrug™ for Alzheimer's disease -

Cytos/Novartis

Immunostimulants Hypersensitivity Discontinued(Preclinical) Unknown route Switzerland Novartis Licensee World Large Pharma, Pharmaceutical Public

Rheumatoid arthritis Discontinued(Preclinical) Unknown route Switzerland

AAV-NGF Gene expression stimulants Alzheimer's disease Phase II Intracranial USA Ceregene Licensee World Biotechnology Private

Alzheimer's disease gene therapy - Ceregene Nerve growth factor stimulants University of California, San Diego Originator USA University N/A

CERE-110 University of California, San Diego Owner USA University N/A

NGF gene therapy

Anti-Abeta mAb Alzheimer's disease Phase II IV Canada, France, Germany, Spain, United Kingdom, USA AC Immune Originator Switzerland Biotechnology Private

Anti-Abeta mAb Alzheimer's disease Phase II SC Canada, France, Germany, Spain, United Kingdom, USA Banner Alzheimers Institute Funder USA Institution N/A

Anti-amyloid-beta monoclonal antibody Alzheimer's disease Preclinical IV Switzerland Genentech Licensee World Large Pharma, Biotechnology Public

MABT5102A National Institutes of Health (USA) Funder USA Institution N/A

RG 7412 Universidad de Antioquia Originator Colombia University N/A

RG7412

Delta(9)-tetrahydrocannabinol - Echo

Pharmaceutical

Alzheimer's disease Phase II PO Netherlands Echo Pharmaceuticals Originator Netherlands Pharmaceutical

Delta(9)-THC - Echo Pharmaceutical Multiple sclerosis Phase II PO Netherlands Echo Pharmaceuticals Owner Netherlands Pharmaceutical

ECP022A (delta9-THC) Pain Phase II PO Netherlands University Medical Centre of Nijmegen Collaborator Netherlands University N/A

Namisol® VU University Medical Center Collaborator Netherlands University N/A

AZD 103 Alzheimer's disease Phase II PO Canada, Spain, USA (Fast Track) Elan Corporation Licensee World Large Pharma, Biotechnology Public

AZD-103 Bipolar disorders (Adjunctive treatment) Phase II PO Bulgaria, Canada, Czech Republic, Lithuania, Romania,

Spain, USA

PPD Collaborator World CRO Public

AZD103 Speranza Therapeutics Sub-licensee World Pharmaceutical

ELND005 Transition Therapeutics Originator Canada Biopharmaceutical Public

Quercinitol Transition Therapeutics Owner Canada Biopharmaceutical Public

Scyllitol

Scyllo-cyclohexanehexol

Scyllo-inositol

EHT 0202 Amyloid precursor protein secretase inhibitors Alzheimer's disease (Adjunctive treatment) Phase II PO France Diaxonhit Owner France Pharmaceutical

EHT 202 GABA A receptor modulators Parkinson's disease Discontinued(I) PO France ExonHit Therapeutics Originator France Technology provider Public

EHT-0202 Type 4 cyclic nucleotide phosphodiesterase

inhibitors

Retinal disorders Discontinued(I) PO France

EHT0202 Vascular dementia Discontinued(Preclinical) PO France

EVP 0015962 Alzheimer's disease Phase II PO USA EnVivo Pharmaceuticals Originator USA Biopharmaceutical Private

EVP-0015962 EnVivo Pharmaceuticals Owner USA Biopharmaceutical Private

EVP-0962

GM6 1 Phosphatidylinositol 3 kinase modulators Amyotrophic lateral sclerosis Phase II IV USA (Fast Track) Genervon Biopharmaceuticals Originator USA Biopharmaceutical Private

GM602 Apoptosis inhibitors Parkinson's disease Phase II IV USA Genervon Biopharmaceuticals Owner USA Biopharmaceutical Private

GM603 Bcl-X protein inhibitors Stroke Phase II IV USA

GM604 Free radical inhibitors Alzheimer's disease (In volunteers) Phase I IV USA

GM605 Insulin receptor modulators Multiple sclerosis (In volunteers) Phase I IV USA

GM606 Nervous system modulators Spinal cord injuries (In volunteers) Phase I IV USA

GM607 Neurogenesis modulators Musculoskeletal disorders Preclinical IV USA

GM608 Proto oncogene protein c akt modulators Huntington's disease Research IV USA

GM609

239512 Alzheimer's disease Phase II PO Chile, European Union, Russia, South Korea GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public

GSK239512 Multiple sclerosis Phase II PO Bulgaria, Germany, Spain, Sweden, United Kingdom GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public

Schizophrenia Phase II PO USA

Alzheimer's disease Phase I PO Australia

933776 Dry age-related macular degeneration Phase II IV USA GlaxoSmithKline Originator United Kingdom Large Pharma, Pharmaceutical Public

Alzheimer's disease vaccine - GlaxoSmithKline Alzheimer's disease Phase I IV Australia, Germany, Norway, Sweden GlaxoSmithKline Owner United Kingdom Large Pharma, Pharmaceutical Public

GSK 933776

GSK-933776

GSK933776A

7beta-hydroxy-epiandrosterone Antioxidants Alzheimer's disease Phase II PO India, Sweden, United Kingdom Hunter-Fleming Originator United Kingdom Biopharmaceutical Private

7beta-OH-EPIA Glucocorticoid receptor antagonists Rheumatoid arthritis Phase I PO United Kingdom Newron Pharmaceuticals Owner Italy Biopharmaceutical Public

HF0220 Inflammatory bowel diseases Discontinued(Preclinical) PO United Kingdom

Psoriasis Discontinued(Preclinical) PO United Kingdom

25

HF 0220 Newron Pharmaceuticals (previously Hunter-

Fleming) is developing HF 0220, an orally

administered 7-hydroxyderivative of

epiandrosterone (7beta-OH-EPIA) with anti-

glucocorticoid and neuroprotective effects, for

the treatment of neurodegenerative disorders

and inflammatory diseases. The company has

carried out phase II trials of HF 0220 for the

treatment of Alzheimer's disease (AD) and a

phase I study in rheumatoid arthritis (RA).

[CONT.]

24

GSK 933776A GSK 933776A is an anti-beta amyloid monoclonal

antibody being developed by GlaxoSmithKline for

intravenous administration in the treatment of

Alzheimer's disease and dry age-related macular

degeneration (geographic atrophy secondary to

age-related macular degeneration). GSK

933776A is in phase I development for the

treatment of AD in Europe and Australia. [CONT.]

Amyloid beta-protein inhibitors

23

GSK 239512 GlaxoSmithKline (GSK) is developing GSK

239512, an orally active histamine H3 receptor

antagonist, for the treatment of cognition

disorders. Phase II trials for the treatment of

Alzheimer's disease and schizophrenia have been

conducted; phase II development in multiple

sclerosis has been initiated in several European

countries.

21

EVP 0962 EnVivo Pharmaceuticals is developing EVP 0962,

an orally available, small molecule, selective

gamma secretase (gamma-secretase) modulator

for the treatment of Alzheimer's disease (AD).

EVP 0962 is brain-permeable and has disease-

modifying potential. Phase II clinical development

is underway in the US. [CONT.]

Amyloid precursor protein secretase modulators

22

GM 6 Genervon is developing a first-in-class peptide

therapeutic, GM 6, for the treatment of

neurological disorders. Genervon discovered

motoneuronotrophic factor (MNTF) that highly

expressed during week nine of embryonic

development, and is a master regulator of the

embryonic nervous system. This discovery led to

the development of GM 6; GM 6 is a six amino

acid analogue of one of the active sites of human

MNTF and one of nine from a patented family of

human master regulators of the nervous system

[CONT.]

20

Etazolate Etazolate is a small molecule, oral compound

belonging to a family of pyrazolopyridines, in

clinical development with Diaxonhit (formerly

ExonHit Therapeutics) in France for the

treatment of neurodegenerative disorders,

including Alzheimer's disease (AD). [CONT.]

19

ELND 005 ELND 005 is a small molecule compound that is

being developed by Speranza Therapeutics for

the treatment of Alzheimer's disease (AD), and

bipolar disorder. Transition Therapeutics

originated ELND 005 and has licensed it to

Speranza worldwide. The orally administered

agent appears to prevent and reverse the

fibrilisation (aggregation into insoluble plaques) of

amyloid-beta (Abeta) peptides in the brain

[CONT.]


18

Dronabinol - Echo

Pharmaceuticals

Echo Pharmaceuticals B.V. is developing a

proprietary tablet formulation of dronabinol for

the treatment of spasticity and pain in patients

with multiple sclerosis (MS), neuropsychiatric

symptoms in Alzheimer's disease (AD) and pain

associated with chronic pancreatitis or post-

surgical abdominal pain. The product is in phase

II clinical development in the Netherlands.

[CONT.]

Cannabinoid receptor agonists

16

CERE 110 Ceregene is developing CERE 110, a gene

therapy for the treatment of Alzheimer's disease

(AD). The therapy employs the company's

proprietary adeno-associated viral (AAV) vector

system to deliver a gene for a neurotrophic

factor, nerve growth factor (NGF), in an attempt

to prevent cell death and reverse cell atrophy.

The therapy is surgically injected into the Nucleus

Basalis of Meynert, a region of the brain in which

cholinergic neurons commonly degenerate in

patients with AD. CERE 110 is in clinical

development for AD in the US. [CONT.]

17

Crenezumab Crenezumab is an anti-amyloid-beta (Abeta)

monoclonal antibody that was identified from a

collaboration between AC Immune Ltd. and

Genentech (Roche) for Alzheimer's disease (AD).

Intravenous and subcutaneous formulations are

in phase II trials with Genentech in the US for the

treatment of AD. [CONT.]


15

CAD 106 Cytos Biotechnology and Novartis in Switzerland

are collaborating in the development of CAD 106

for the potential treatment of Alzheimer's

disease. CAD 106 treatment aims to generate

antibodies against the beta-amyloid protein and

inhibit beta-amyloid plaque formation. CAD 106

consists of two components, the Immunodrug™

carrier Qb coupled with a fragment of the beta-

amyloid-protein. [CONT.]

13

BAN 2401 BioArctic Neuroscience and Eisai are jointly

developing BAN 2401, a humanised monoclonal

antibody originated by BioArctic, for the

treatment of Alzheimer's disease. BAN 2401

selectively binds to and eliminates amyloid beta-

peptide protofibrils, a soluble aggregate of

amyloid beta-peptide thought to play a role in

the development of Alzheimer's disease. [CONT.]


14

Bapineuzumab Bapineuzumab is a humanised monoclonal

antibody that is designed to specifically target

amyloid-beta (Abeta) in the brain. Pfizer and

JANSSEN Alzheimer Immunotherapy are co-

developing this product for the treatment of

Alzheimer's disease (AD). The product was

undergoing phase III development for AD

worldwide as an intravenous (IV) formulation.

However, development of the IV formulation was

discontinued [CONT.]

AZD 3480 Alzheimer's disease Phase II PO Czech Republic, Romania, Slovakia, Ukraine, USA R. J. Reynolds Tobacco Company Originator USA Company

AZD-3480 Attention-deficit hyperactivity disorder Discontinued(II) PO USA Targacept Originator USA Biopharmaceutical Public

AZD3480 Cognition disorders Discontinued(II) PO Canada, USA

RJR 1734 Cognition disorders (In volunteers) Discontinued(I) PO Japan

RJR-1734

TC 01734

TC 1734

TC-1734

Ladostigil hemitartrate Cholinesterase inhibitors Alzheimer's disease Phase II PO Austria, Croatia, Germany, Serbia, Spain Avraham Pharmaceuticals Licensee Israel Pharmaceutical Private

TV 3326 Monoamine oxidase inhibitors Mild cognitive impairment Phase II PO Austria, Germany, Israel Hebrew University of Jerusalem Originator Israel University N/A

TV-3326 Hebrew University of Jerusalem Owner Israel University N/A

TV3326 Rappaport Institute Collaborator Israel Institution N/A

Yissum Research Development Company Technology Transfer Israel Technology Transfer Private

LU AE58054 Alzheimer's disease (Adjunctive treatment) Phase II PO Australia, Canada, Czech Republic, Germany, Italy, Poland,

Spain

Asterand plc Technology Provider USA Pharmaceutical Public

LUAE 58054 Cognition disorders (Adjunctive treatment:Cognitive

impairment associated with schizophrenia (CIAS))

Phase II PO Belgium, France, Hong Kong, Italy, Poland, Taiwan,

Thailand

Eli Lilly Originator USA Large Pharma, Pharmaceutical Public

SGS 518 Cognition disorders Phase II PO USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public

SGS-518 Lundbeck A/S Licensee World Large Pharma, Pharmaceutical Public

SGS518 Otsuka Pharmaceutical Sub-licensee Asia, Canada, Europe, Japan, USA Pharmaceutical Private

SNX-001 Alzheimer's disease Phase II PO Mexico SeneXta Therapeutics Licensee World Biopharmaceutical

SNX001 Alzheimer's disease Phase I PO Germany The University of Texas at El Paso Originator USA

Cognition disorders Preclinical PO USA The University of Texas at El Paso Owner USA

Mitoglitazone™ Mitochondrial protein stimulants Alzheimer's disease Phase II PO USA Metabolic Solutions Development Company Originator USA Pharmaceutical Private

MSDC-0160 MTOR protein inhibitors Type 2 diabetes mellitus Phase II PO USA Metabolic Solutions Development Company Owner USA Pharmaceutical Private

Polycystic kidney disease Preclinical PO USA PKD Foundation Collaborator USA Institution N/A

University of Illinois at Chicago Collaborator USA University N/A

NIC5 15 Alzheimer's disease Phase II PO USA Humanetics Corporation Licensee USA Pharmaceutical Private

NIC5-15 Mount Sinai School of Medicine Originator USA University N/A

Mount Sinai School of Medicine Owner USA University N/A

Alzheimer's disease Phase II PO Finland, Spain Orion Originator Finland Pharmaceutical Public

Raynaud's disease Discontinued(II) PO United Kingdom Orion Owner Finland Pharmaceutical Public

Schizophrenia No development reported(II) PO Europe

PBT-2 Alzheimer's disease (Early-stage disease) Phase II PO Australia, Sweden Prana Biotechnology Originator Australia Biotechnology Public

PBT2 Huntington's disease (Early-stage disease, Mid-stage

disease)

Phase II PO Australia, USA Prana Biotechnology Owner Australia Biotechnology Public

Huntington's disease (In volunteers) Phase I PO Netherlands

PF-05212377 Alzheimer's disease (Adjunctive treatment) Phase II PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public

PF-5212377 Alzheimer's disease (In volunteers) Phase I PO France Wyeth Originator USA Large Pharma, Pharmaceutical Public

SAM-760

WYE-103760

Alzheimer's disease Phase II PO South Korea PuriMED Originator South Korea Biotechnology Private

PuriMED Owner South Korea Biotechnology Private

(+)-(3aR)-phenserine Acetylcholinesterase inhibitors Alzheimer's disease Phase II PO USA Cenomed BioSciences Licensee World Biopharmaceutical Private

(+)-phenserine Alpha-synuclein inhibitors Mild cognitive impairment Phase II PO USA Massachusetts General Hospital Collaborator USA Hospital N/A

Posiphen® Amyloid beta-protein precursor inhibitors Parkinson's disease Phase II PO USA National Institute on Aging Originator USA Institution N/A

Tau protein inhibitors Poisoning Preclinical PO USA National Institutes of Health (USA) Originator USA Institution N/A

QR Pharma Licensee World Biotechnology

Raptor Pharmaceutical Corp Originator USA Pharmaceutical Public

EVT-302 Alzheimer's disease (Adjunctive treatment, Combination

therapy)

Phase II PO Australia, Canada, Czech Republic, France, Germany, Italy,

Poland, South Korea, Spain, Sweden, USA

Evotec AG Licensee World Pharmaceutical Public

EVT302 Alzheimer's disease Phase I PO Japan Roche Originator Switzerland Large Pharma, Pharmaceutical Public

RG-1577 Alzheimer's disease (In volunteers) Phase I PO Netherlands Roche Owner Switzerland Large Pharma, Pharmaceutical Public

RG1577 Smoking withdrawal Discontinued(II) PO Germany Roche Sub-licensee World Large Pharma, Pharmaceutical Public

RO-4602522 Smoking withdrawal Discontinued(I) PO Finland, United Kingdom

RO4602522

659032 Alzheimer's disease Phase II PO Bulgaria, Germany, Italy, Norway, Spain, Sweden GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public

38

Rilapladib Rilapladib, an oral inhibitor of lipoprotein-

associated phospholipase A2 (Lp-PLA2), was

discovered as part of a collaboration between

GlaxoSmithKline (GSK) and Human Genome

Sciences (now a GSK subsidiary). Phase I

development appears to have been completed

and the compound has moved into phase II

studies in patients with atherosclerosis in the

USA. Phase II clinical development is also

underway for Alzheimer's disease. [CONT.]

1-alkyl-2-acetylglycerophosphocholine esterase

inhibitors

37

RG 1577 Roche is developing RG 1577 (also known as EVT

302), a selective and reversible monoamine

oxidase B (MAO-B) inhibitor, for the treatment of

Alzheimer's disease. Preclinical studies of RG

1577 showed a superior safety profile to that of

already marketed MAO-B inhibitors, and

improved tolerability compared with current

treatments for nicotine dependence. [CONT.]

Monoamine oxidase B inhibitors

35

PM 012 The South Korean-based company PuriMED is

developing a herbal-based medicine called PM

012, which is intended for the prevention of

dementia, specifically that related to Alzheimer's

disease. While the specific components of PM 012

are unknown, the company has indicated that

this herbal medicine has the potential to increase

the learning ability in young people and

prevented forgetfulness in elderly subjects

[CONT.]

PM012 tablet - PuriMED

36

R-phenserine QR Pharma, under a licence from Raptor

Pharmaceutical Corp. (formerly TorreyPines

Therapeutics), is developing R-phenserine, the R-

enantiomer (positive isomer) of phenserine, for

the treatment of Alzheimer's disease (AD) and

Parkinson's disease (PD). The compound has also

been licensed to Cenomed BioSciences, who will

develop it for the treatment of poisoning

following exposure to organophosphorous nerve

agents [CONT.]

34

PF 5212377 Pfizer is developing PF 5212377, a small

molecule, serotonin 6 receptor (5-HT6)

antagonist for the treatment of Alzheimer's

disease. Serotonin 6 receptor antagonists may

improve deficits in learning and memory by

increasing levels of the neurotransmitters

acetylcholine and glutamate. PF 5212377 was

originally developed by Wyeth as WYE 103760,

also referred to as SAM 760. [CONT.]

Serotonin 6 receptor antagonists

33

PBT 2 PBT 2 is a second-generation, small molecule,

metal protein-attenuating compound (MPAC) that

is in clinical development with Prana

Biotechnology for the treatment of Alzheimer's

disease (AD) and Huntington's disease (HD). It is

an 8-hydroxyquinoline derivative that targets the

interaction between metals and beta-amyloid

(Abeta) in the synapse. [CONT.]

Chelating agents

31

NIC 515 Humanetics Corporation and Mount Sinai School

of Medicine are developing NIC 515 as an oral

agent for the treatment of Alzheimer's disease

(AD). NIC 515, a small naturally occurring

molecule, is a potent insulin sensitiser. The

compound also prevents certain peptides from

aggregating to form beta amyloid plaques

associated with Alzheimer's disease and improves

cognitive function in mice with AD type

neuropathology and memory impairment [CONT.]

Amyloid precursor protein secretase inhibitors

32

ORM 12741 Orion Pharma is developing an oral alpha2c

adrenergic receptor antagonist, ORM 12741, for

the treatment of Alzheimer's disease. A phase II

trial in this indication has been completed in

Finland and Spain. Phase II trial development in

the treatment of Raynaud's disease was

discontinued. ORM 12741 was also in phase II

development for the treatment of schizophrenia.

[CONT.]

ORM-12741 Alpha 2c adrenergic receptor antagonists

29

Methanesulfonyl fluoride SeneXta Therapeutics is developing

methanesulfonyl fluoride, SNX 001, as a novel,

long-acting, oral inhibitor of acetylcholinesterase

(AChE) for the treatment of Alzheimer's disease

and post stroke cognitive impairment.

Methanesulfonyl fluoride was originally developed

by the University of Texas at El Paso. Initial

exploratory non-GLP (Good Laboratory Practice)

trials (phase I and II) in the Alzheimer's disease

indication were completed in Mexico [CONT.]

Acetylcholinesterase inhibitors

30

MSDC 0160 Metabolic Solutions Development Company is

developing MSDC 0160 (Mitoglitazone™), a once

daily, oral peroxisome proliferator-activated

receptor gamma (PPARgamma)-sparing insulin

sensitiser, for the treatment of type 2 diabetes

mellitus, Alzheimer's disease and polycystic

kidney disease. MSDC 0160 is undergoing phase

II development for type 2 diabetes mellitus and

Alzheimer's disease in the US [CONT.]

28

Lu AE 58054 Lu AE 58054 is an orally active, serotonin 6 (5-

HT6) receptor antagonist, which is being

developed by Lundbeck for the treatment of

cognitive impairment associated with

schizophrenia (CIAS) and for Alzheimer's disease.

The serotonin 6 receptor is primarily found in

areas of the brain involved in cognition. [CONT.]


27

Ladostigil Ladostigil is a cholinesterase and brain-selective

monoamine oxidase (MAO) inhibitor that is being

developed by Avraham Pharmaceuticals as an

oral treatment for Alzheimer's disease and mild

cognitive impairment. The agent is designed to

provide a combination of the improved cognitive

function exhibited by inhibitors of cholinesterase

(i.e. [CONT.]

26

Ispronicline Ispronicline is a CNS-selective, nicotinic receptor

partial agonist that is being developed by

Targacept (formerly a subsidiary of R.J. Reynolds

Tobacco Company) for the treatment of

Alzheimer's disease (AD). This orally active, small

molecule is selective for the alpha4beta2-

containing nicotinic receptor subtypes in the

brain, which have been associated with nicotinic

cholinergic modulation of learning and memory

processes [CONT.]

Alpha4 beta2 nicotinic receptor agonists

GSK 659032 Atherosclerosis Phase II PO USA Human Genome Sciences Originator USA Biopharmaceutical Public

GSK659032

SB 659032

SB-659032

RVX 000222 Apolipoprotein A I stimulants Acute coronary syndromes Phase II PO Argentina, Brazil, European Union, Russia, USA Cedars-Sinai Health System Collaborator USA Institution N/A

RVX-000222 Bromodomain and extraterminal domain protein

inhibitors

Atherosclerosis Phase II PO Argentina, Brazil, European Union, Russia, USA Resverlogix Corporation Originator Canada Biotechnology Public

RVX-208 Low HDL cholesterol Phase II PO South Africa Resverlogix Corporation Owner Canada Biotechnology Public

RVX000222 Prediabetic-state Phase II PO Australia

RVX208 Alzheimer's disease Phase I PO USA

Alzheimer's disease Phase II PO United Kingdom Servier Originator France Pharmaceutical Private

Servier Owner France Pharmaceutical Private

SAR110894 Alzheimer's disease Phase II PO Australia, Canada, France, Germany, Italy, Poland, Portugal,

Spain, USA

Sanofi Owner France Large Pharma, Pharmaceutical Public

SAR110894D sanofi-aventis Originator France Large Pharma, Pharmaceutical Public

Cogane™ Brain derived neurotrophic factor agonists Alzheimer's disease Phase II PO United Kingdom Phytopharm Originator England Pharmaceutical Public

PYM-50028 Glial cell line-derived neurotrophic factor agonists Parkinson's disease (Early-stage disease) Phase II PO Canada, Czech Republic, France, Germany, Hungary,

Poland, Romania, Serbia, United Kingdom, USA

Phytopharm Owner England Pharmaceutical Public

PYM50028 Neuron stimulants Amyotrophic lateral sclerosis Preclinical PO United Kingdom

Glaucoma Preclinical PO United Kingdom

742457 Alzheimer's disease (Combination therapy:Add-on to

donepezil)

Phase II PO Argentina, Australia, Canada, Chile, European Union, USA GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public

GSK 742457 Alzheimer's disease Phase II PO Chile, Croatia, European Union, Mexico, New Zealand,

Russia, South Africa, South Korea

GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public

SB-742457 Alzheimer's disease (In volunteers) Phase I PO USA

Alzheimer's disease Phase II PO China Shanghai Green Valley Pharmaceutical Originator China Manufacturer

Shanghai Green Valley Pharmaceutical Owner China Manufacturer

Alzheimer's disease Phase II Unknown route Europe Digna Biotech Originator Spain Biotechnology Private

University of Navarra Originator Spain University N/A

VEL 015 Alzheimer's disease (Early-stage disease) Phase II PO Australia Velacor Therapeutics Originator Australia Pharmaceutical

VEL-015 Velacor Therapeutics Owner Australia Pharmaceutical

VEL015

ST101 Alzheimer's disease Phase II PO Canada, USA Sonexa Therapeutics Licensee USA Biopharmaceutical Private

ZSET 1446 Essential tremor Phase II PO USA Zenyaku Kogyo Originator Japan Pharmaceutical Private

ZSET-1446 Zenyaku Kogyo Owner Japan Pharmaceutical Private

ZSET1446

T-817MA Alzheimer's disease Phase II PO USA Toyama Chemical Originator Japan Pharmaceutical Public

T817MA Alzheimer's disease Phase I PO Japan Toyama Chemical Owner Japan Pharmaceutical Public

TC-0569 Cognition disorders (Adjunctive treatment:In patients with

schizophrenia)

Phase II PO Eastern Europe, USA Targacept Originator USA Biopharmaceutical Public

TC-5619 Cognition disorders (Adjunctive treatment:In patients with

schizoprenia)

Phase II PO India Targacept Owner USA Biopharmaceutical Public

TC-5619-238 Alzheimer's disease Phase I PO USA

TC5619 Attention-deficit hyperactivity disorder Discontinued(II) PO USA

PF 04494700 Advanced glycosylation end-product receptor

antagonists

Alzheimer's disease Phase II PO USA (Fast Track) TransTech Pharma Originator USA Pharmaceutical Private

PF-04494700 Amyloid inhibitors Diabetic nephropathies Discontinued(II) PO Canada TransTech Pharma Owner USA Pharmaceutical Private

PF-4494700

TTP488

Abeta immunotherapeutic conjugate Alzheimer's disease Phase II IM France, Germany, Japan, Spain, USA Agenus Technology Provider USA Biotechnology Public

AAC 001 Boston Biomedical Research Institute Technology Provider USA Institution N/A

AAC-001 Elan Corporation Originator Ireland Large Pharma, Biotechnology Public

AAC001 JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical

ACC 001 Pfizer Owner USA Large Pharma, Pharmaceutical Public

ACC-001 Wyeth Originator USA Large Pharma, Pharmaceutical Public

ACC00151

Vanutide cridificar Pfizer and JANSSEN Alzheimer Immunotherapy

are co-developing vanutide cridificar, an

immunoconjugate vaccine based around amyloid-

beta (Abeta) peptide, for the treatment of

Alzheimer's disease (AD). The vaccine, which is

administered as an intramuscular injection, is

generated through the conjugation of small N-

terminal peptide fragments of Abeta to a non-

toxic diphtheria mutant carrier protein, CRM197

[CONT.]

Immunostimulants

50

TTP 488 TTP 488 is an orally administered, small molecule

drug candidate that is being developed by

TransTech Pharma for the treatment of

Alzheimer's disease. TTP 488 is an antagonist of

the receptor for advanced glycation end (RAGE)

products, and appears to inhibit amyloid

fibrillogenesis. The compound was undergoing

joint research by TransTech Pharma and Pfizer

up until the latter ceased its activities for this

compound [CONT.]

49

TC 5619 Targacept is developing TC 5619, an orally

administered small molecule that is highly

selective for the alpha7 nicotinic acetylcholine

receptor (alpha7 nAChR). The alpha7 nAChR is

associated with sensory gating and cognition, and

compounds that modulate this target could play a

role in the protection of neuronal cells from

deterioration and death. [CONT.]

Alpha7 nicotinic acetylcholine receptor agonists

48

T 817MA T 817MA is an orally available, benzothiophenyl

derivative with neuroprotective activity that is

being developed by Toyama Chemical for the

treatment of Alzheimer's disease (AD). This

neurotrophic agent prevents amyloid-beta

(Abeta)-induced neurodegeneration and

promotes neurite outgrowth. Preclinical studies

suggest T 817MA may improve cognition by

reducing oxidative stress. [CONT.]


46

Sodium selenate - Velacor

Therapeutics

Velacor Therapeutics is developing sodium

selenate, as an oral capsule, for the treatment of

Alzheimer's disease. The compound acts to

restore the activity of protein phosphatase 2a

(PP2A), which is responsible for cleaving

phosphatase from tau. Tau stablises the

microtubule transport system in neurons and

hyperphosphorylation of tau causes tau tangles

seen in Alzheimer's disease. [CONT.]

Protein phosphatase 2A stimulants

47

ST 101 Sonexa Pharmaceuticals, under an exclusive

license from Zenyaku Kogyo in Japan, is

developing an orally active, first-in-class, small-

molecule compound ST 101, an azaindolizinone

derivative, for the treatment of Alzheimer's

disease (AD) and essential tremor. ST 101 has

been demonstrated to stimulate acetylcholine

release in the hippocampus and cerebral coretex,

and has also reduced cognitive impairment in

animal models [CONT.]

Acetylcholine stimulants

44

Sodium oligomannurarate Shanghai Green Valley Pharmaceutical is

developing sodium oligomannurarate for the

treatment of Alzheimer's disease. A phase II

clinical trial is assessing the efficacy and

tolerability of sodium oligomannurarate capsules

in approximately 252 subjects with mild to

moderate Alzheimer's disease from China

(NCT01453569).

Sodium oligo-mannurarate Undefined mechanism

45

Sodium phenylbutyrate - Digna

Biotech

Digna Biotech is developing the small-molecule

compound sodium phenylbutyrate (4-PBA) as a

therapy for Alzheimer's disease in clinical trials in

Europe. The University of Navarra in Pamplona,

Spain, is also involved in the development of this

agent. Digna Biotech is a spin-off company of the

Centre for Applied Medical Research of the

University of Navarra. [CONT.]

4-PBA Histone deacetylase inhibitors

42

Sarsasapogenin Phytopharm is developing sarsasapogenin, an

orally active, small molecule, non-peptide, nerve

growth factor stimulant, for the treatment of

neurodegenerative disorders, including

Alzheimer's disease (AD), Parkinson's disease

(PD) and amyotrophic lateral sclerosis (ALS).

Additional potential indications include glaucoma,

vascular dementia, mild cognitive impairment,

diabetic neuropathy and neuropsychiatric

disorders, such as schizophrenia, depression,

anxiety and epilepsy [CONT.]

43

SB 742457 SB 742457 is an oral serotonin (5-HT)6 receptor

antagonist in phase II development with

GlaxoSmithKline (GSK) for the treatment of

Alzheimer's disease. SB 742457 undergone trials

as a monotherapy, and as an add-on treatment

to donepezil.


40

S 38093 S 38093 is a histamine H3 receptor antagonist

that is being developed by Servier for the

treatment of Alzheimer's disease. Phase II

development of the agent is ongoing in the UK,

and is expected to soon be initiated in a number

of other countries throughout the EU and

globally.

S38093 Histamine H3 receptor antagonists

41

SAR 110894 Sanofi (formerly sanofi-aventis) is developing

SAR 110894, a histamine H3 receptor antagonist,

for the treatment of Alzheimer's disease. The H3

receptor is a G-protein coupled receptor that is

predominantly expressed in the central nervous

system. These autoreceptors negatively regulate

the release of neurotransmitters including

dopamine, norepinephrine, acetylcholine and

histamine and are believed to play a role in the

regulation of feeding, cognition, arousal, pain and

endocrine systems [CONT.]

Histamine H3 receptor antagonists

39

RVX 208 Resverlogix is developing RVX 208, an orally

available, small-molecule, bromodomain and

extraterminal domain (BET) protein inhibitor,

which increases apolipoprotein AI (ApoA-I) and

HDL-cholesterol levels. The first-in-class

compound was developed using Resverlogix's

NexVas™ technology, and is designed to treat

cardiovascular disorders, including

atherosclerosis, cerebrovascular disease and

hypertension, and Alzheimer's disease (AD)

[CONT.]

38

Rilapladib Rilapladib, an oral inhibitor of lipoprotein-

associated phospholipase A2 (Lp-PLA2), was

discovered as part of a collaboration between

GlaxoSmithKline (GSK) and Human Genome

Sciences (now a GSK subsidiary). Phase I

development appears to have been completed

and the compound has moved into phase II

studies in patients with atherosclerosis in the

USA. Phase II clinical development is also

underway for Alzheimer's disease. [CONT.]

1-alkyl-2-acetylglycerophosphocholine esterase

inhibitors

Active beta-amyloid immunotherapeutic

conjugateCRM 197

CRM197

Peptide-CRM Conjugate

PF-05236806

PF-5236806

TD 5108 Constipation Phase II PO USA Alfa Wassermann SpA Collaborator Italy Pharmaceutical Private

TD-5108 Gastroparesis Phase II PO USA Theravance Originator USA Biopharmaceutical Public

TD5108 Alzheimer's disease Phase I PO USA Theravance Owner USA Biopharmaceutical Public

VI-1121 Alzheimer's disease (Adjunctive treatment) Phase II Unknown route USA VIVUS Originator USA Pharmaceutical Public

VI1121 VIVUS Owner USA Pharmaceutical Public

Alzheimer's disease I/II Parenteral Scandinavia AC Immune Originator Switzerland Biotechnology Private

AC Immune Owner Switzerland Biotechnology Private

Bayer HealthCare Pharmaceuticals Collaborator Germany Pharmaceutical Public

APH 0703 Alzheimer's disease I/II IV Bahamas Aphios Corporation Originator USA Biopharmaceutical Private

APH-0703 Cognition disorders I/II IV Bahamas Aphios Corporation Owner USA Biopharmaceutical Private

Bryosomes™ Alzheimer's disease Preclinical IV USA

Bryostatin 1-containing phospholipid nanosomes

(Bryosomes™) - Aphios

Alzheimer's disease Preclinical PO USA

Bryostatin-1 - Aphios Cognition disorders Preclinical IV USA

Nanoencapsulated APH 0703 Cognition disorders Preclinical PO USA

Oesophageal cancer (New delivery system) Preclinical Parenteral USA

beta secretase inhibitor - Eli Lilly Alzheimer's disease I/II PO Italy, Japan, Netherlands, Spain, USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public

LY2886721 Alzheimer's disease (In volunteers) Phase I PO USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public

ARC 029 Alzheimer's disease I/II Unknown route Europe Archer Pharmaceuticals Originator USA Pharmaceutical Private

ARC029 Alzheimer's disease Phase I Unknown route USA Archer Pharmaceuticals Owner USA Pharmaceutical Private

Alzheimer's disease I/II SC Canada Regenera Pharma Originator Israel Pharmaceutical Private

Chronic wounds I/II Topical Israel Regenera Pharma Owner Israel Pharmaceutical Private

Burns Preclinical Topical Israel

Neurodegenerative disorders Preclinical Parenteral Israel

Wyeth (Pfizer) and JANSSEN Alzheimer

Immunotherapy are collaborating on the

development of AAB 003, an intravenously

administered monoclonal antibody that targets

and inhibits beta-amyloid (Abeta) peptide, for the

treatment of Alzheimer's disease (AD). The

product is in phase I clinical development in the

US and South Korea.

AAB-003 Alzheimer's disease Phase I IV South Korea, USA Elan Corporation Originator Ireland Large Pharma, Biotechnology Public

The compound was initially being developed by

Wyeth and Elan. [CONT.]

AAB003 JANSSEN Alzheimer Immunotherapy Owner Ireland Pharmaceutical

PF-05236812 Pfizer Owner USA Large Pharma, Pharmaceutical Public

Wyeth Originator USA Large Pharma, Pharmaceutical Public

AAD-2004 Amyloid beta-protein inhibitors Alzheimer's disease Phase I Unknown route European Union AmKor Pharma Collaborator USA Biotechnology Private

AAD2004 Antioxidants Amyotrophic lateral sclerosis Phase I Unknown route European Union GNT Pharma Owner South Korea Pharmaceutical Public

Dinoprostone antagonists Parkinson's disease Phase I Unknown route European Union Neurotech Pharmaceuticals Originator South Korea Pharmaceutical Public

Free radical scavengers Toyota Tsusho Corporation Market Licensee Japan Company Public

Prostaglandin synthase inhibitors

AADvac1 Immunostimulants Alzheimer's disease Phase I SC Austria Axon Neuroscience Originator Slovakia Biotechnology

Alzheimer's disease vaccine - Axon Neuroscience Tau protein modulators Axon Neuroscience Owner Slovakia Biotechnology

ABP-102 Alzheimer's disease Phase I Parenteral Europe Abiogen Pharma Originator Italy Pharmaceutical Private

ABP102 Abiogen Pharma Owner Italy Pharmaceutical Private

62

ABP 102 Abiogen Pharma is developing ABP 102 in clinical

trials in Europe for the treatment of Alzheimer's

disease (AD). ABP 102 is an abzyme; these

comprise anti-beta-amyloid (Abeta) monoclonal

antibodies fused to a peptide hydrolase

(protease). Such catalytic monoclonal antibodies

are designed as carriers of proteins with protease

activity for selective lysis of beta-amyloid 1-42

protein (Abeta1-42), a [CONT.]


61

AADvac 1 Axon Neuroscience is developing AADvac 1, a tau

peptide-KLH conjugate active vaccine for the

treatment of Alzheimer's disease. The vaccine

targets misfolded tau protein, and is expected to

prevent cognitive decline through reducing

neurofibrillary tangles, removing

hyperphosphorylated tau protein and reducing

the amount of oligomerised and insoluble

pathological tau in the brain. [CONT.]

59

AAB 003 Amyloid beta-protein inhibitors

60

AAD 2004 AAD 2004 is a sulfasalazine-derived small

molecule that is being developed by GNT Pharma

in South Korea and its US subsidiary, AmKor

Pharma for the treatment of Alzheimer's disease

(AD), Parkinson's disease (PD) and amyotrophic

lateral sclerosis (ALS). The drug provides

neuroprotection via both antioxidative and anti-

inflammatory effects, as well as the inhibition and

reduction of beta-amyloid (Abeta) peptide levels

and Abeta plaque formation [CONT.]

58

RPh 201 Regenera Pharma is developing RPh 201, a

proprietary formulation of a well-defined and

characterised botanical drug, for the treatment of

neurodegenerative diseases, burns and chronic

wounds. RPh 201 is being developed with the

company's novel, proprietary extraction and

purification processes. RPh 201 has

demonstrated unprecedented neuroregeneration

in well-established animal models of stroke and

dementia [CONT.]

RPh201 Undefined mechanism

56

LY 2886721 Eli Lilly is developing LY 2886721, an orally

available, small molecule inhibitor of the BACE1

protein, for the treatment of patients with

Alzheimer's disease (AD). Cleavage of the

amyloid precursor protein by BACE1 is one of the

necessary steps in the formation of amyloid beta,

and so inhibition of the enzyme is expected to

halt progression of the disease. [CONT.]

57

Nilvadipine - Archer

Pharmaceuticals

Archer Pharmaceuticals is developing a

proprietary formulation of nilvadipine for the

treatment of Alzheimer's disease (AD). This drug

may be the first member of a new class of drugs

known as soluble amyloid reducing/clearing

agents (SARC). Nilvadipine, a calcium channel

blocker, is widely used in the treatment of

hypertension (since 1991) and studies suggest it

has pro-cognitive functions. [CONT.]

Calcium channel antagonists

55

Bryostatin 1 - Aphios Aphios is a biopharmaceutical company

developing a natural therapeutic, called

bryostatin 1, for certain cancers and CNS

disorders. Bryostatin 1 is a protein kinase C

activator that has been isolated from sea moss

(Bugula neritina), which is found off the coast of

California, USA. Bryostatin 1 is an anticancer

agent has entered more than 35 phase I and II

clinical trials by the National Cancer Institute

(NCI) and others for melanomas, lymphomas and

other cancers. [CONT.]

Protein kinase C stimulants

53

VI 1121 VIVUS is developing VI 1121, a compound for the

treatment of Alzheimer's disease. The mechanism

of action and route of administration are

undisclosed. The company is conducting a phase

II clinical study in the US.

Undefined mechanism

54

ACI 24 AC Immune is developing ACI 24 for the

treatment of Alzheimer's disease. The compound

was developed using the company's antigen

technology (SupraAntigen™) platform which

induces changes in the conformation of misfolded

proteins, shifting the equilibrium in favour of

benign forms. Incorrect processing of amyloid

precursor protein (APP) generates the beta

amyloid protein, the main component of the

plaques found in the brains of Alzheimer's

patients [CONT.]

Immunostimulants

52

Velusetrag Velusetrag is a selective serotonin-4 (5-HT4)

receptor agonist that is being developed by

Theravance as a once-daily oral prokinetic for the

treatment of chronic constipation. Development is

also in progress for Alzheimer's disease. The drug

was developed in collaboration with

GlaxoSmithKline, through the application of

multivalent drug design from the company's drug

discovery programme. [CONT.]

Serotonin 4 receptor agonists

51

Vanutide cridificar Pfizer and JANSSEN Alzheimer Immunotherapy

are co-developing vanutide cridificar, an

immunoconjugate vaccine based around amyloid-

beta (Abeta) peptide, for the treatment of

Alzheimer's disease (AD). The vaccine, which is

administered as an intramuscular injection, is

generated through the conjugation of small N-

terminal peptide fragments of Abeta to a non-

toxic diphtheria mutant carrier protein, CRM197

[CONT.]

Immunostimulants

Alzheimer's disease Phase I Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

AbbVie Owner USA Biopharmaceutical Public

AD 03 Amyloid beta-protein inhibitors Alzheimer's disease Phase I SC Austria AFFiRiS Originator Austria Biotechnology Private

AD03 Immunostimulants AFFiRiS Owner Austria Biotechnology Private

Affitope-AD03 GlaxoSmithKline Licensee World Large Pharma, Pharmaceutical Public

Alzheimer AD03

MimoVax™

Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO USA ProteoTech Originator USA Biotechnology Private

Tau protein inhibitors ProteoTech Owner USA Biotechnology Private

Tasly Pharmaceutical Group Licensee China Pharmaceutical Private

ANAVEX 19-144 prodrug Calcium channel antagonists Alzheimer's disease (In volunteers) Phase I PO Germany ABX-CRO Collaborator Germany CRO Private

ANAVEX2-73 Muscarinic M2 receptor antagonists Epilepsy (In volunteers) Phase I Unknown route Germany Anavex Life Sciences Originator Switzerland Biopharmaceutical Public

Muscarinic M3 receptor antagonists Stroke (In volunteers) Phase I Unknown route Germany Anavex Life Sciences Owner Switzerland Biopharmaceutical Public

NMDA receptor antagonists Alzheimer's disease (Combination therapy) Preclinical Parenteral France Genesis Biopharma Collaborator Canada Biopharmaceutical Private

Sigma-1 receptor agonists Alzheimer's disease (Monotherapy) Preclinical Parenteral Germany

Sodium channel antagonists

ARC 031SR Alzheimer's disease Phase I Unknown route USA Archer Pharmaceuticals Originator USA Pharmaceutical Private

ARC031 Archer Pharmaceuticals Owner USA Pharmaceutical Private

ARC031 SR

Alzheimer's disease Phase I PO USA Astellas Pharma US Originator USA Company

Astellas Pharma US Owner USA Company

Alzheimer's disease Phase I PO USA Avera Pharmaceuticals Originator Usa Pharmaceutical Private

Cognition disorders Phase I PO USA Avera Pharmaceuticals Owner Usa Pharmaceutical Private

Avineuro Pharmaceuticals (US) is developing the

small molecule AVN 322, a serotonin 6 receptor

antagonist, for the treatment of Alzheimer's

disease. The compound was in phase I

development.

Alzheimer's disease Phase I Unknown route USA Avineuro Pharmaceuticals Licensee World Pharmaceutical Private

Avineuro Pharmaceuticals licensed AVN 322 from

ChemDiv.

ChemDiv Originator USA CRO Private

ChemDiv Owner USA CRO Private

[11C]AZD 2184 Alzheimer's disease (Diagnosis) Phase I IV Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

[11C]AZD2184 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

AZD2184 Navidea Biopharmaceuticals Licensee USA Biopharmaceutical Public

[11C]AZD 2995 Alzheimer's disease (Diagnosis) Phase I IV Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

[11C]AZD2995 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

AZD2995 Navidea Biopharmaceuticals Licensee USA Biopharmaceutical Public

AZD-3293 Alzheimer's disease Phase I PO USA Astex Pharmaceuticals Originator USA Pharmaceutical Public

AZD3293 AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

Alzheimer's disease (Early-stage disease) Phase I PO Europe Janssen Pharmaceuticals Licensee USA Pharmaceutical Public

Shionogi Originator Japan Large Pharma, Pharmaceutical Public

Shionogi Owner Japan Large Pharma, Pharmaceutical Public

2434074 Alzheimer's disease Phase I PO Unknown Eli Lilly Originator USA Large Pharma, Pharmaceutical Public

LSN 2434074 Eli Lilly Owner USA Large Pharma, Pharmaceutical Public

LY 2434074

LY-2434074

A beta-amyloid converting enzyme (BACE1)

inhibitor is in development with Merck and Ligand

Pharmaceuticals for the treatment of Alzheimer's

disease. A phase I multi-dose trial was completed

in the US. According to Ligand's research

pipeline, the inhibitor compound is still in phase I

development.

Alzheimer's disease Phase I Unknown route USA Ligand Pharmaceuticals Owner USA Biotechnology Public

76

BACE1 protein inhibitor -

Ligand/Merck

BACE1 protein inhibitors

75

BACE1 protein inhibitor - Eli

Lilly

Eli Lilly is developing an inhibitor of beta

secretase (BACE1 protein) for the treatment of

patients with Alzheimer's disease. The company

aimed to design a molecule that could penetrate

the blood-brain barrier and limit the formation of

beta-amyloid (Abeta)40/42 peptides. BACE1

protein catalyzes the first step of the two-step

amyloid precursor protein (APP) cleavage

process, which in turn leads to the formation of

Abeta40/42 peptides [CONT.]


73

AZD 3293 AstraZeneca is developing AZD 3293, an orally

administered small-molecule for the treatment of

Alzheimer's disease. AZD 3293 inhibits the

amyloid precursor protein secretase, beta-

secretase, which is a key protein involved in the

formation of myelin sheaths in peripheral nerve

cells and in the pathogenesis of Alzheimer's

disease. The enzyme inhibition prevents the build

up of beta-amyloid to slow or stop the

progression of the disease [CONT.]


74

BACE inhibitor -

Janssen/Shionogi

Janssen Pharmaceuticals and Shionogi are

developing an oral beta-secretase (BACE;

amyloid precursor protein secretase) inhibitor for

the treatment of prodromal (early-stage)

Alzheimer's disease. A phase I trial is in progress

in Europe. [CONT.]


71

AZD 2184 AstraZeneca is developing AZD 2184 ([11C]AZD

2184) as an in vivo imaging agent for use in

positron emission tomography (PET) in the

diagnosis of Alzheimer's disease (AD). This

candidate 11C-radiolabelled, PET ligand

selectively binds amyloid-beta (Abeta) peptides

to enable visualisation of amyloid plaque deposits

in the brain that are characteristic of AD. [CONT.]

Positron-emission tomography enhancers

72

AZD 2995 AstraZeneca is developing AZD 2995 ([11C]AZD

2995) as an in vivo imaging agent for use in

positron emission tomography (PET) in the

diagnosis of Alzheimer's disease (AD). This

candidate 11C-radiolabelled, PET ligand

selectively binds amyloid-beta (Abeta) peptides

to enable visualisation of amyloid plaque deposits

in the brain that are characteristic of AD. [CONT.]

Positron-emission tomography enhancers

69

AV 965 Avera Pharmaceuticals is developing the

serotonin (5-HT)1A receptor antagonist AV 965

for schizophrenia-associated cognitive impairment

(cognition disorders) and Alzheimer's disease in

the US. AV 965 was originated by Eli Lilly who

licensed the drug and supporting intellectual

property to Avera Pharmaceuticals in 2002.

[CONT.]

AV965 Serotonin 1A receptor antagonists

70

AVN 322 AVN-322 Serotonin 6 receptor antagonists

67

ARC 031 Archer Pharmaceuticals is developing ARC 031, a

member of a new class of drugs known as soluble

amyloid reducing/clearing agents (SARC), for the

treatment of Alzheimer's disease. The parent

compound of this molecule is nilvadipine, a

calcium channel blocker that is widely used in the

treatment of hypertension (since 1991).

Importantly, ARC 031 exerts its effect without

calcium channel blocking. [CONT.]

Undefined mechanism

68

ASP 0777 Astellas Pharma is developing ASP 0777 as a oral

treatment for dementia associated with

Alzheimer's disease. The mechanism of action for

ASP 0777 has not been disclosed. Phase Ib

development is underway in the US.

ASP0777 Undefined mechanism

66

ANAVEX 2-73 Anavex Life Sciences is developing ANAVEX 2-73,

a small molecule for the treatment of Alzheimer's

disease (AD), epilepsy and stroke. The drug was

developed using the company's proprietary

SIGMACEPTOR™ platform. Various formulations

of the drug have been tested preclinically, but

only the oral formulation is being assessed in

clinical trials. A phase Ia single ascending dose

trial of ANAVEX 2-73 in AD has been completed

in Germany [CONT.]

64

Affitope AD03 AFFiRiS and GlaxoSmithKline are collaborating on

the development of affitope AD03, a vaccine

candidate for the treatment of Alzheimer's

disease. The vaccine has been customised using

AFFiRiS' Affitope platform technology (Affitom®)

and is designed to induce cross-reactive

antibodies against a native antigen, without

producing a systemic immune response. [CONT.]

65

Alzheimer's disease therapeutic -

ProteoTech

ProteoTech is developing an oral small molecule

therapeutic (Exebryl-1®), targeting amyloid-beta

(Abeta) protein fibrillogenesis, for the treatment

of Alzheimer's disease (AD). In addition, Exebryl-

1® has been shown to reduce tau protein

formation as well as exhibit anti-inflammatory

properties such as astrocytosis and microgliosis.

[CONT.]

Exebryl-1®

63

ABT 957 AbbVie is developing ABT 957, a calpain inhibitor

for potential use in the treatment of Alzheimer's

disease (AD). The over activation of calpain, a

calcium-dependent cysteine protease, is believed

to play a role in the pathophysiology of several

neurodegenerative disorders, including AD. In

particular, the etiological pathway points to the

hyperphosphorylation of the microtubule-

associated protein tau and the subsequent

aggregation of tau filaments causing the

formation of neurofibrillary tangles [CONT.]

ABT-957 Calpain inhibitors

The BACE1 enzyme is a key protein implicated in

the pathogenesis of Alzheimer's disease. [CONT.]

Merck & Co Collaborator USA Large Pharma, Pharmaceutical Public

Pharmacopeia Originator USA Biopharmaceutical Public

BAY85-8101 Alzheimer's disease (Diagnosis:Trial completed) Phase I IV Netherlands, Sweden Bayer HealthCare Pharmaceuticals Originator Germany Pharmaceutical Public

F-18 FEDAA1106 Multiple sclerosis (Diagnosis:Trial completed) Phase I IV Australia, Sweden Piramal Healthcare Owner World Pharmaceutical Public

F18-FEDAA1106

ZK 6032924

Biogen Idec is developing BIIB 037, a fully

human antibody against beta-amyloid, for the

treatment of Alzheimer's disease. Phase I clinical

development is underway in the US.

BART Alzheimer's disease Phase I IV USA Biogen Idec Licensee USA Large Pharma, Biotechnology Public

This lead candidate is a product of Biogen Idec

and Neurimmune Therapeutics'

neurodegenerative disease antibody research

programme [see separate profile].

BIIB037 Neurimmune Therapeutics Originator Switzerland Biotechnology Private

Neurimmune Therapeutics Owner Switzerland Biotechnology Private

Bisnorcymcerine Amyloid beta-protein precursor inhibitors Alzheimer's disease Phase I PO USA National Institute on Aging Originator USA Institution N/A

BNC Butyrylcholinesterase inhibitors Cognition disorders Preclinical PO USA National Institutes of Health (USA) Originator USA Institution N/A

Poisoning Discontinued(Preclinical) PO USA QR Pharma Licensee World Biotechnology

Raptor Pharmaceutical Corp Owner World Pharmaceutical Public

BLU8499 Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO Canada Asclepios Bioresearch (UK) Funder United Kingdom Investor Private

NRM-8499 GABA A receptor agonists BELLUS Health Originator Canada Biopharmaceutical Public

NRM8499 BELLUS Health Owner Canada Biopharmaceutical Public

BMS-241027 Tau protein inhibitors Alzheimer's disease Phase I IV USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

Microtubule stabilizer Tubulin modulators Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

ATG Z1 Alzheimer's disease Phase I IV USA Astellas Pharma Licensee World Large Pharma, Pharmaceutical Public

ATG-Z1 CoMentis Originator USA Biopharmaceutical Private

CTS-21166 CoMentis Owner USA Biopharmaceutical Private

DB959 Peroxisome proliferator-activated receptor delta

agonists

Alzheimer's disease (In volunteers) Phase I PO USA Bayer HealthCare Pharmaceuticals Originator USA Pharmaceutical Public

DB959Na Peroxisome proliferator-activated receptor

gamma agonists

Dyslipidaemias (In volunteers) Discontinued(I) PO USA Bayer HealthCare Pharmaceuticals Owner USA Pharmaceutical Public

T3D-959 Type 2 diabetes mellitus (In volunteers) Discontinued(I) PO USA T3D Therapeutics Licensee World Pharmaceutical Private

Peroxisome proliferator-activated receptor alpha

agonists

Alzheimer's disease Phase I PO USA Dainippon Sumitomo Pharma Originator Japan Large Pharma, Pharmaceutical Public

Peroxisome proliferator-activated receptor

gamma agonists

Type 2 diabetes mellitus Phase I PO USA Dainippon Sumitomo Pharma Owner Japan Large Pharma, Pharmaceutical Public

Sunovion Pharmaceuticals Licensee USA Pharmaceutical Public

DWP 09031 is an orally administered, small

molecule inhibitor of amyloid beta (Abeta) protein

aggregation, being developed by Daewoong

Pharmaceutical for the treatment of Alzheimer's

disease. Phase I clinical development is underway

in South Korea.

Alzheimer's disease (In volunteers) Phase I PO South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public

DWP 09031 is available for licensing. Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public

E-2012 Alzheimer's disease (In volunteers:Trial completed) Phase I PO USA Eisai Co Ltd Originator Japan Large Pharma, Pharmaceutical Public

E2012 Eisai Co Ltd Owner Japan Large Pharma, Pharmaceutical Public

Eisai is developing an amyloid precursor protein

secretase modulator, E 2212, for the treatment

of Alzheimer's disease (AD).

E-2212 Alzheimer's disease (In volunteers) Phase I PO USA Eisai Inc Originator USA Pharmaceutical Public

The company has completed a US-based,

randomised, double-blind, placebo-controlled,

single ascending dose phase I trial, which

investigated the safety, tolerability,

pharmacokinetics and pharmacodynamics of

single oral doses of E 2212 in 60 healthy subjects

(NCT012212590)<REF [CONT.]

E2212 Eisai Inc Owner USA Pharmaceutical Public

Alzheimer's disease Phase I PO USA Eisai Inc Originator USA Pharmaceutical Public

Eisai Inc Owner USA Pharmaceutical Public

GE Healthcare Collaborator United Kingdom Technology provider Public

ECB-AD Alzheimer's disease Phase I Intracerebral Sweden NsGene Originator Denmark Biotechnology Private

ECT-AD NsGene Owner Denmark Biotechnology Private

ECT-NGF

89

Encapsulated cell therapy -

Alzheimers's disease - NsGene

NsGene A/S is developing a cell therapy product

for the treatment of Alzheimer's disease. The cell

therapy product is based on human retinal

pigment epithelial parent cell line (NGC-0295)

obtained from the organ donor that has been

genetically modified to stably secrete human

nerve growth factor (NGF) and encapsulated in

the polyvinylalcohol cylindrical matrix. [CONT.]

Neuron stimulants

87

E 2212 Amyloid precursor protein secretase modulators

88

E 2609 Eisai is developing E 2609, a beta-secretase-1

(BACE 1) inhibitor, for the treatment of

Alzheimer's disease (AD). The drug reduced total

beta-amyloid, resulting in symptomatic

improvement as well as disease modification.

Phase I development is underway in the US.

[CONT.]

E2609 BACE1 protein inhibitors

85

DWP 09031 DWP09031 Amyloid beta-protein inhibitors

86

E 2012 E 2012 is an orally available, amyloid precursor

protein secretase (gamma-secretase) modulator

that is being developed by Eisai for the treatment

of Alzheimer's disease (AD). It was discovered

from the derivatives of seed compounds from

Eisai's compound library using multi-dimensional

analysis. The protease gamma-secretase cleaves

the amyloid precursor protein (APP) to produce

amyloid-beta (Abeta) protein, a major

component of AD-related plaques in the brain

causing impaired neural function. E 2012 is

undergoing clinical development for AD in the US.

[CONT.]

Amyloid precursor protein secretase modulators


83

DB 959 DB 959 is a highly selective, non-

thiazolidinedione, first-in-class dual peroxisome

proliferator activated receptor delta/gamma

(PPARdelta/gamma) agonist that has been

acquired by T3D Therapeutics and will be

developed as a once-daily oral therapy for

Alzheimer's disease (AD) and other CNS

disorders. [CONT.]

84

DSP 8658 Dainippon Sumitomo Pharma and Sunovion

Pharmaceuticals are developing DSP 8658, an

orally active peroxisome proliferator-activated

receptor alpha/gamma (PPARalpha/gamma)

agonist, for the treatment of type 2 diabetes

mellitus and Alzheimer's disease. DSP 8658

emerged as a lead compound from Dainippon's

research and development programme. [CONT.]

DSP-8658

81

BMS 241027 Bristol-Myers Squibb is developing BMS 241027,

a small molecule, microtubule stabiliser for the

treatment of Alzheimer's disease. The company's

approach is to prevent the production of

abnormal tau protein, which is implicated in the

decline in cognition of patients with Alzheimer's

disease. Phase I development of BMS 240127 is

underway in the US.

82

CTS 21166 CTS 21166 is a small molecule and orally

bioavailable, amyloid precursor protein secretase

(beta-secretase) inhibitor, which is being

developed by CoMentis and its licensing partner,

Astellas, as a disease-modifying treatment for

Alzheimer's disease (AD). In preclinical studies,

CTS 21166 exhibits excellent efficacy, selectivity,

brain penetration and pharmacological activity.

The agent is in clinical development in the US.

[CONT.]

79

Bisnorcymserine Bisnorcymserine is an orally available, small

molecule inhibitor of butyrylcholinesterase, an

enzyme that appears to be elevated in amyloid-

beta plaques in the brains of patients with

Alzheimer's disease (AD). Bisnorcymserine also

acts to inhibit the formation of amyloid-beta

precursor protein (Abeta-PP) in cell culture and in

rats, which indicates potential for the prevention

of the formation of amyloid plaques [CONT.]

80

BLU 8499 BELLUS Health (formerly known as Neurochem

Inc.) is developing a prodrug of tramiprosate,

BLU 8499, for the treatment of Alzheimer's

disease. This agent increases brain exposure to

tramiprosate, and is therefore expected to

improve cognitive function and clinical outcomes.

A phase I trial has been completed in Canada.

[CONT.]

78

BIIB 037 Amyloid beta-protein inhibitors

76

BACE1 protein inhibitor -

Ligand/Merck


77

BAY 858101 BAY 858101 is an IV-administered, 18F-labelled

radiopharmaceutical used with positron emission

tomography (PET) for the diagnosis of disorders

associated with neuroinflammation, including

multiple sclerosis and Alzheimer's disease.

Piramal Healthcare acquired the programme from

Bayer HealthCare Pharmaceuticals (formerly

Bayer Schering Pharma). Two phase I clinical

trials have been completed. [CONT.]

Undefined mechanism

NsG0202

GSK-2647544 Alzheimer's disease (In volunteers) Phase I PO Australia GlaxoSmithKline Originator United Kingdom Large Pharma, Pharmaceutical Public

GSK2647544 GlaxoSmithKline Owner United Kingdom Large Pharma, Pharmaceutical Public

HPP854 Alzheimer's disease Phase I PO USA High Point Pharmaceuticals Owner World Pharmaceutical Private

TTP 854 TransTech Pharma Originator USA Pharmaceutical Private

TTP-854

TTP854

HupA transdermal Acetylcholinesterase inhibitors Alzheimer's disease Phase I Transdermal China Mayo Clinic Originator USA Institution N/A

Qian ceng ta transdermal Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Topical USA Mayo Clinic Owner USA Institution N/A

Qian-ceng-ta transdermal Antioxidants Alzheimer's disease Preclinical Transdermal USA Neuro-Hitech Licensee World Pharmaceutical Public

XEL 001HG NMDA receptor antagonists Xel Pharmaceuticals Collaborator USA Pharmaceutical Private

XEL 001HP Xel Pharmaceuticals Technology Provider USA Pharmaceutical Private

Xiangxue Pharmaceutical Collaborator China Pharmaceutical

Janssen Research & Development is developing

JNJ 54861911 for the oral treatment of

Alzheimer's disease. Phase I clinical development

in healthy volunteers is in progress in Belgium.

Alzheimer's disease (In volunteers) Phase I PO Belgium Janssen Research & Development Originator USA Pharmaceutical Public

In May 2013, Janssen Research & Development

initiated a phase I clinical trial to evaluate the

safety, tolerability and pharmacodynamics of

multiple ascending oral doses of JNJ 54861911 in

healthy elderly volunteers (NCT01887535)

[CONT.]

Janssen Research & Development Owner USA Pharmaceutical Public

Alzheimer's disease (In volunteers) Phase I PO USA Kareus Therapeutics Originator Switzerland Pharmaceutical Private

Kareus Therapeutics Owner Switzerland Pharmaceutical Private

Eli Lilly is developing LY 3002813, a biological

agent for the treatment of Alzheimer's disease. A

phase I clinical trial of intravenous and

subcutaneous formulations is underway in the US

and Japan.

LY3002183-SC Alzheimer's disease Phase I IV Japan, USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public

In May 2013, Eli Lilly initiated a randomised,

double-blind, placebo-controlled phase I trial to

investigate the safety, tolerability and

pharmacokinetics of LY 3002813 in patients with

mild to moderate Alzheimer's disease

(NCT01837641) [CONT.]

LY3002813 Alzheimer's disease Phase I SC Japan, USA Eli Lilly Owner USA Large Pharma, Pharmaceutical Public

LY3002813-IV

N3pG-Asz Monoclonal Antibody

CDD 0102 Amyloid beta-protein inhibitors Alzheimer's disease Phase I PO USA Mithridion Licensee World Biopharmaceutical

CDD 0102J Muscarinic M1 receptor agonists Alzheimer's disease Preclinical Transdermal USA University of Toledo Originator USA University N/A

CDD-0102 Progressive supranuclear palsy Preclinical PO USA University of Toledo Owner USA University N/A

CDD-0102-J Schizophrenia Preclinical PO USA

CDD-0102J Schizophrenia Preclinical Transdermal USA

MCD-386

MCD-386 Forte

MCD-386 Forte/Transderm

MCD-386 Transderm

MCD-386CR

Neurostem® Alzheimer's disease Phase I Intracerebral South Korea Medipost Originator South Korea Biotechnology Private

Neurostem®-AD Medipost Owner South Korea Biotechnology Private

Merck is developing MK 3328, a fluoro-

azabenzoxazole compound, as a positron

emission tomography (PET) tracer for the

diagnosis of neurodegenerative disorders,

including Alzheimer's disease. Phase I

development is ongoing in Belgium.

[18F]MK-3328 Alzheimer's disease (Diagnosis) Phase I IV Belgium Merck & Co Originator USA Large Pharma, Pharmaceutical Public

The direct, non-invasive detection of beta-

amyloid (Abeta) plaque deposits using PET

imaging is a promising method to accurately

diagnose Alzheimer's disease (AD) prior to the

onset of severe cognitive decline [CONT.]

[18F]MK3328 Merck & Co Owner USA Large Pharma, Pharmaceutical Public

MK-3328

MK3328

CP 609754 Alzheimer's disease Phase I PO USA AstraZeneca Sub-licensee United Kingdom Large Pharma, Pharmaceutical Public

LNK-754 Neurodegenerative disorders Phase I PO USA Link Medicine Corporation Licensee USA Pharmaceutical Private

Bladder cancer Discontinued(I) PO USA OSI Pharmaceuticals Originator USA Biotechnology Public

OSI Pharmaceuticals Owner USA Biotechnology Public

Alzheimer's disease (Diagnosis) Phase I Unknown route European Union, USA Takeda Originator Japan Large Pharma, Pharmaceutical Public

Diagnostic tests Phase I Unknown route European Union, USA Zinfandel Pharmaceuticals Originator USA Biotechnology Private

PQ-912 Alzheimer's disease (In volunteers) Phase I PO Switzerland Probiodrug Originator Germany Pharmaceutical Private

101

PQ 912 Probiodrug is developing PQ 912, an orally active

small molecule, for the treatment of Alzheimer's

disease. PQ 912 inhibits the enzymatic activity of

glutaminyl-peptide cyclotransferase (glutaminyl

cyclase), a metalloenzyme that catalyses the

formation of pyroglutamate-modified amyloid-

beta, a highly toxic amyloid-b.eta variant that is

involved in the development and progression of

Alzheimer's disease [CONT.]

Glutaminyl-peptide cyclotransferase inhibitors

100

Pioglitazone companion

diagnostic

Takeda is utilising Zinfandel Pharmaceuticals'

TOMM40 biomarker assay to identify high risk

individuals as candidates for clinical trials

investigating the use of pioglitazone for the

prevention of Alzheimer's disease. The TOMM40

biomarker is associated with an increased risk of

developing Alzheimer's disease, and this assay

can be used to gauge which older individuals at

high risk of disease onset should be enrolled in

clinical trials [CONT.]

AD4833/TOMM40

98

MK 3328

99

OSI 754 OSI 754 is an oral inhibitor of farnesyl

transferase, an enzyme of crucial importance in

the ras signalling pathway. This compound was

originally developed by OSI Pharmaceuticals in

collaboration with Pfizer and subsequently

licensed to Link Medicine Corporation for all

indications, excluding oncology. AstraZeneca

have acquired the rights to this programme.

Farnesyltranstransferase inhibitors

97

Mesenchymal stem cell therapy

for neurological disorders -

Medipost

Medipost is developing a product (called

Neurostem®) based on adult mesenchymal stem

cells (MSC) derived from umbilical cord blood for

the treatment of Alzheimer's disease,

amyotrophic lateral sclerosis (ALS) and stroke,

via recovery of functionality and tissues of the

CNS. The MSCs in Neurostem® are believed to

promote proliferation and differentiation of neuro-

progenitor cells within the host thereby restoring

functionality of the tissue [CONT.]

Tissue replacements

96

MCD 386 Mithridion is developing MCD 386, a highly

selective muscarinic M1 receptor agonist, for the

treatment of Alzheimer's disease (AD) and

cognitive impairment in schizophrenia. This small

molecule drug is designed to improve the brain

functions of memory and cognition, as well as to

stop or delay AD-related pathology that cause

neuronal cell death. Phase I development of oral

MCD 386 controlled release in AD is underway in

the US [CONT.]

95

LY 3002813 Undefined mechanism

93

JNJ 54861911 JNJ-54861911 Undefined mechanism

94

KU 046 Kareus Therapeutics is developing KU 046 for the

treatment of Alzheimer's disease. The compound

was discovered using Kareus' bioenergetics and

Karlect chemistry platforms, which combines

currently marketed drugs and GRAS molecules to

produce proprietary chemical entities that have

an improved therapeutic index. KU 046 targets

pathways upstream of amyloid beta peptide

production and significantly improved cognition in

a number of preclinical models [CONT.]

KU-046 Amyloid beta-protein modulators

92

Huperzine A - Neuro-Hitech/Xel Neuro-Hitech and Xel Pharmaceuticals is

developing huperzine A in transdermal patch

(XEL 001HP) and topical gel (XEL 001HG)

formulations, using Xel's drug delivery

technology, for the treatment of Alzheimer's

disease (AD). Phase I development of the patch

formulation is underway in China and an IND

filing is expected in the US soon. Preclinical

development of the gel formulation is underway

in the US. [CONT.]

90

GSK 2647544 GlaxoSmithKline is developing oral lipoprotein-

associated phospholiapse A2 (Lp-PLA2) inhibitor,

GSK 2647544, for the treatment of Alzheimer's

disease. A phase I trial was completed in

Australia.

Phospholipase A2 inhibitors

91

HPP 854 High Point Pharmaceuticals (a spin-off company

from TransTech Pharma) is developing HPP 854,

an orally active, small molecule compound that

inhibits BACE1, the enzyme responsible for

amyloid-beta (Abeta) generation, for potential

use in the treatment of Alzheimer's disease.

BACE (beta-site amyloid precursor protein-

cleaving enzyme) is a type-1 transmembrane

protein and an aspartyl protease with beta-

secretase activity [CONT.]


89

Encapsulated cell therapy -

Alzheimers's disease - NsGene

NsGene A/S is developing a cell therapy product

for the treatment of Alzheimer's disease. The cell

therapy product is based on human retinal

pigment epithelial parent cell line (NGC-0295)

obtained from the organ donor that has been

genetically modified to stably secrete human

nerve growth factor (NGF) and encapsulated in

the polyvinylalcohol cylindrical matrix. [CONT.]

Neuron stimulants

PQ912 Probiodrug Owner Germany Pharmaceutical Private

Alzheimer's disease Phase I PO USA EPIX Pharmaceuticals Originator USA Biopharmaceutical Public

Cognition disorders Phase I PO USA Unknown Owner USA Company

Obesity Phase I PO USA

R-1500 Alzheimer's disease Phase I Unknown route Europe Roche Originator Switzerland Large Pharma, Pharmaceutical Public

R1500 Roche Owner Switzerland Large Pharma, Pharmaceutical Public

R-1577 Alzheimer's disease Phase I PO Europe Roche Originator Switzerland Large Pharma, Pharmaceutical Public

R1577 Roche Owner Switzerland Large Pharma, Pharmaceutical Public

RG7129 Alzheimer's disease (In volunteers) Phase I PO France, USA Roche Originator Switzerland Large Pharma, Pharmaceutical Public

RO 5508887 Roche Owner Switzerland Large Pharma, Pharmaceutical Public

RO5508887

RQ-00000009 Acetylcholine stimulants Alzheimer's disease Phase I PO Japan Pfizer Originator USA Large Pharma, Pharmaceutical Public

RQ-9 Amyloid beta-protein inhibitors Pfizer Owner USA Large Pharma, Pharmaceutical Public

RQ9 Serotonin 4 receptor agonists RaQualia Pharma Licensee World Pharmaceutical Private

CX 1632 AMPA receptor agonists Alzheimer's disease Phase I Unknown route France Cortex Pharmaceuticals Originator USA Pharmaceutical Public

CX1632 Nerve growth factor stimulants Dementia Phase I Unknown route France Cortex Pharmaceuticals Owner USA Pharmaceutical Public

S47445 Mild cognitive impairment Phase I Unknown route France Servier Licensee World Pharmaceutical Private

University of California at Irvine Technology Provider USA University N/A

Anti-protofibrillar AB mAb Alzheimer's disease Phase I IV Sweden Sanofi Originator France Large Pharma, Pharmaceutical Public

SAR228810 Alzheimer's disease Phase I SC Sweden Sanofi Owner France Large Pharma, Pharmaceutical Public

Nitric oxide mimetic (sGC-1061) Amyloid beta-protein inhibitors Alzheimer's disease Phase I Unknown route USA Alzheimers Drug Discovery Foundation Funder USA Company

Nomethiazoles (NO-chimera prodrugs) - sGC

Pharma

Nitric oxide stimulants Alzheimer's disease Preclinical Unknown route USA Queens University Originator Canada University N/A

sGC-1061 Tau protein inhibitors sGC Pharma Licensee USA Biotechnology

Sustained-release sGC-1061 University of Illinois Originator USA University N/A

M1 Alzheimer's disease Phase I PO Switzerland Suven Life Sciences Originator India Company

M1 of SUVN-502 Attention-deficit hyperactivity disorder Phase I PO Switzerland Suven Life Sciences Owner India Company

Cognition disorders Phase I PO Switzerland

Parkinson's disease Phase I PO Switzerland

Schizophrenia Phase I PO Switzerland

TAK-070 Alzheimer's disease (In the elderly, In volunteers) Phase I PO Japan Takeda Originator Japan Large Pharma, Pharmaceutical Public

TAK070 Takeda Owner Japan Large Pharma, Pharmaceutical Public

University of Tokyo Licensee Japan University N/A

Alzheimer's disease Phase I Unknown route USA Theravance Originator USA Biopharmaceutical Public

Gastrointestinal disorders Phase I Unknown route USA Theravance Owner USA Biopharmaceutical Public

Alzheimer's disease Phase I SC USA Pfizer Licensee World Large Pharma, Pharmaceutical Public

TransTech Pharma Originator USA Pharmaceutical Private

TransTech Pharma Owner USA Pharmaceutical Private

Alzheimer's disease Phase I IM Taiwan, USA United Biomedical Originator USA Biopharmaceutical Private

United Biomedical Owner USA Biopharmaceutical Private

V-950 Alzheimer's disease Phase I IM USA CSL Technology Provider Australia Large Pharma, Biopharmaceutical Public

V950 Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Merck & Co Owner USA Large Pharma, Pharmaceutical Public

114

UB 311 United Biomedical (UBI) is developing UB 311, a

liquid intramuscular delivered amyloid beta

protein inhibitor vaccine, for the treatment of

mild-to-moderate Alzheimer's disease. Phase I

development is underway in Taiwan and the US.

UBITh AD immunotherapeutic vaccine (UB 311) -

United Biomedical


115

V 950 V 950 is a vaccine product that is being

developed by Merck & Co. for the treatment of

Alzheimer's disease (AD). Merck is developing a

preparation of V 950 using Iscomatrix® adjuvant

technology in-licensed from CSL. This adjuvant is

expected to improve Merck's vaccine by

producing more potent and durable immune

responses against certain AD antigens. [CONT.]

Immunostimulants

112

TD 8954 Theravance is developing a CNS-penetrant

serotonin 4 receptor (5-HT4) agonist, TD 8954,

to ameliorate the cognitive impairment associated

with Alzheimer's disease (AD). Serotonin 4

receptors are widely expressed in the

hippocampus, amygdala and prefrontal cortex, all

of which receive substantial cholinergic input, and

are involved in cognition. [CONT.]

TD-8954 Serotonin 4 receptor agonists

113

TTP 4000 TTP 4000 is a large molecule fusion between the

ligand binding domains of an extracellular portion

of the advanced glycation end product receptor

(RAGE) and immunoglobulin G under

development with TransTech Pharma as a

treatment for Alzheimer's disease. RAGE has

been identified as a receptor for amyloid-beta

and other amyloidogenic proteins including serum

amyloid A and amylin, which play a critical role in

the pathophysiology of Alzheimer's disease

[CONT.]

TTP4000 Advanced glycosylation end product inhibitors

111

TAK 070 The University of Tokyo is developing TAK 070 for

the treatment of Alzheimer's disease (AD). This

orally active, non-peptidic human beta secretase

(beta-secretase, BACE) inhibitor was discovered

by Takeda. The company had conducted

preclinical development for AD in Japan, prior to

licensing the compound to the University of

Tokyo. [CONT.]


109

sGC 1061 sGC 1061 is a lead compound from a new class of

compounds, called nomethiazoles (or NO-chimera

prodrugs), which is in development with sGC

Pharma as a potential therapy for Alzheimer's

disease (AD) and age-related cognitive

impairment (memory disorders). The

nomethiazoles therapeutic class was initially

defined by Professor Greg Thatcher while at

Queen's University; he subsequently went to

work at the University of Illinois College of

Pharmacy [CONT.]

110

SUVN 502 Suven Life Sciences is developing an oral

formulation of SUVN 502, a selective serotonin 6

(5-HT6) receptor antagonist, for the symptomatic

treatment of Alzheimer's disease, and other

disorders of memory and cognition such as

schizophrenia, Parkinson's disease and attention

deficit hyperactivity disorder (ADHD). [CONT.]


107

S 47445 Les Laboratories Servier (Servier) is developing S

47445 for the treatment of neurodegenerative

disorders. S 47445 is an AMPA receptor agonist,

which was developed using Cortex's Ampakine®

technology and was later licensed to Servier

under a research collaboration and license

agreement between the two companies. Servier

originally had the rights to develop three of

Cortex's Ampakine® compounds under the

licensing agreement, but it discontinued

development of the other two in favour of S

47445. Phase I development of S 47445 is

underway in France. [CONT.]

108

SAR 228810 Sanofi is developing SAR 228810 for the

treatment of Alzheimer's disease. It is a

monoclonal antibody that inhibits amyloid

fibrillogenesis. The company has described the

drug as an 'anti-protofibrillar AB mAb'. Phase I

development of intravenous and subcutaneous

formulations is underway in Sweden.

Amyloid inhibitors

105

RG 7129 Roche is developing RG 7129, an orally

administered inhibitor of beta-secretase (BACE-

1), for the treatment of Alzheimer's disease. RG

7129 is undergoing phase I clinical development

in the US and France.


106

RQ 00000009 RaQualia is developing RQ 00000009, an oral,

small molecule serotonin 4 receptor (5-HT4)

partial agonist, for the treatment of Alzheimer's

disease (AD). RQ 00000009 is designed to

improve memory and cognitive function by

increasing acetylcholine secretion, and also

modify the pathophysiological condition of AD by

decreasing amyloid beta-protein production.

[CONT.]

103R 1500 R 1500, an enzyme inhibitor, in clinical

development with Roche for the potential

treatment of Alzheimer's disease in Europe.

Enzyme inhibitors

104R 1577 Roche is developing R 1577, an enzyme inhibitor,

for potential utility in the treatment of

Alzheimer's disease in Europe

Enzyme inhibitors

102

PRX 07034 PRX 07034, a small-molecule serotonin 6 (5-HT6)

receptor antagonist, is in development for the

treatment of Alzheimer's disease, obesity and

cognitive impairment associated with

schizophrenia. The compound was originally in

development with EPIX Pharmaceuticals.

However, rights to the the compound have been

sold to an undisclosed company. [CONT.]

PRX-07034 Serotonin 6 receptor antagonists

101

PQ 912 Probiodrug is developing PQ 912, an orally active

small molecule, for the treatment of Alzheimer's

disease. PQ 912 inhibits the enzymatic activity of

glutaminyl-peptide cyclotransferase (glutaminyl

cyclase), a metalloenzyme that catalyses the

formation of pyroglutamate-modified amyloid-

beta, a highly toxic amyloid-b.eta variant that is

involved in the development and progression of

Alzheimer's disease [CONT.]

Glutaminyl-peptide cyclotransferase inhibitors

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