Alzheimer's Disease (Preclinical & Research) · ALRT 4204 The Michael J. Fox Foundation for Parkinsons Research Collaborator USA Institution N/A ALRT-4204 ALRT4204 IRX-4204 IRX4204

Indication Phase Route Country Name Role Country Type OwnershipAGN 194204 Prostate cancer Phase II PO USA Allergan Originator USA Large Pharma, Pharmaceutical Public

AGN-194204 Alzheimer's disease Preclinical PO USA Io Therapeutics Owner World Biopharmaceutical Private

AGN194204 Parkinson's disease Preclinical PO USA Mount Sinai School of Medicine Collaborator USA University N/A

ALRT 4204 The Michael J. Fox Foundation for Parkinsons Research Collaborator USA Institution N/A

ALRT-4204

ALRT4204

IRX-4204

IRX4204

NRX 194204

NRX 4204

NRX-194204

NRX-4204

NRX194204

NRX4204

VTP 194204

VTP-194204

VTP194204

Adipose stem cell therapies - RNL BIO Facial hemiatrophy Phase II Parenteral South Korea Asan Medical Center Collaborator South Korea Hospital N/A

Adult-derived stem cell therapies - RNL BIO Osteoarthritis Phase II Intra articular South Korea RNL BIO Originator South Korea Biotechnology

Astrostem Thromboangiitis obliterans Phase II Parenteral South Korea RNL BIO Owner South Korea Biotechnology

Autologous adipose stem cells - RNL BIO Intervertebral disc degeneration I/II Parenteral South Korea RST Biomedikal Sanayi Licensee Turkey Biotechnology

Cancerstem Osteonecrosis I/II Parenteral South Korea University of Newcastle upon Tyne Collaborator United Kingdom University N/A

Fat-derived stem cell therapies - RNL BIO Spinal cord injuries I/II Intraspinal South Korea

Lipostem-DM Spinal cord injuries I/II Intrathecal South Korea

Lipostem-Femoran Spinal cord injuries I/II IV South Korea

Mesenchymal stem cell therapies - RNL BIO Liver disorders Clinical IV Asia

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

hCNS-SC Age-related macular degeneration I/II Intraocular USA Oregon Health & Science University Collaborator USA University N/A

HuCNS-SC Spinal cord injuries I/II Intraosseous Switzerland ReNeuron Technology Provider United Kingdom Biopharmaceutical Public

HuCNS-SC cells Pelizaeus-Merzbacher disease Phase I Intracerebral USA StemCells Originator USA Biotechnology Public

HuCNS-SC® Alzheimer's disease Preclinical Parenteral USA StemCells Owner USA Biotechnology Public

Neurodegenerative disorders stem cell therapy -

StemCells

Stroke Preclinical Parenteral USA University of California at Irvine Collaborator USA University N/A

Neuronal ceroid lipofuscinosis Discontinued(I) Intracerebral USA

Haemophilia B I/II IV USA ARIAD Pharmaceuticals Collaborator USA Pharmaceutical Public

Neuronal ceroid lipofuscinosis Phase I Intracranial USA ARIAD Pharmaceuticals Technology Provider USA Pharmaceutical Public

Age-related macular degeneration Preclinical Ophthalmic USA ReGenX Biosciences Originator USA Biopharmaceutical

Alzheimer's disease Preclinical Parenteral USA ReGenX Biosciences Owner USA Biopharmaceutical

Haemophilia A Preclinical Parenteral USA St. Jude Childrens Research Hospital Collaborator USA Hospital N/A

Hypercholesterolaemia Preclinical Parenteral USA University of Pennsylvania Medical Center Collaborator USA University N/A

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 G protein-coupled receptor modulators Asthma (Combination therapy) I/II Inhalation USA Revalesio Originator USA Biotechnology Private

RNS60 Ion channel modulators Asthma Phase I IV USA Revalesio Owner USA Biotechnology Private

Myocardial infarction (In volunteers) Phase I IV USA Rush University Collaborator USA University N/A

Alzheimer's disease Preclinical Unknown route USA

Multiple sclerosis Preclinical IV USA

Parkinson's disease Preclinical Unknown route USA

AEN 100 Antioxidants Amyotrophic lateral sclerosis I/II PO USA Adeona Pharmaceuticals Originator USA Biotechnology Public

AEN-100 Free radical scavengers Alzheimer's disease Preclinical PO USA Synthetic Biologics Owner USA Biotechnology Public

AEN-100/AEN-200 Glutathione peroxidase stimulants

reaZin™

Zinc cysteine - Adeona

Adult neural stem cells - Neuralstem Amyotrophic lateral sclerosis Phase I Intraspinal USA China Medical University Hospital Collaborator Taiwan Hospital N/A

HNSC Alzheimer's disease Preclinical Unknown route USA CJ Cheiljedang Corp. Collaborator South Korea Biopharmaceutical

HSSC Amyotrophic lateral sclerosis Preclinical Intraspinal Taiwan Emory University Collaborator USA University N/A

NSI 566 Brain injuries Preclinical Unknown route USA Neuralstem Originator Usa Company

NSI 566RSC Cerebral palsy Preclinical Unknown route USA Neuralstem Owner Usa Company

NSI-566 Diabetic neuropathies Preclinical Unknown route USA University of California, San Diego Technology Provider USA University N/A

NSI-566RSC Huntington's disease Preclinical Unknown route Germany University of Freiburg Collaborator Germany University N/A

NSI566 Lysosomal storage diseases Preclinical Unknown route USA

Multiple sclerosis Preclinical Unknown route USA

Optic neuritis Preclinical Unknown route USA

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 Major depressive disorder Phase I PO USA Neuralstem Originator Usa Company

NSI-189 phosphate Alzheimer's disease Preclinical PO USA Neuralstem Owner Usa Company

NSI189 Brain injuries Preclinical Unknown route USA Summit Pharmaceuticals International Corporation Licensee Japan Company

Cognition disorders Preclinical PO USA

Neurodegenerative disorders Preclinical PO USA

Post-traumatic stress disorders Preclinical PO USA

Stroke Preclinical Unknown route USA

CNS disorders (In volunteers) Phase I IV Canada, USA Northwestern University Originator USA University N/A

Alzheimer's disease Preclinical PO Canada Northwestern University Owner USA University N/A

Rheumatoid arthritis Preclinical PO Canada Transition Therapeutics Licensee Canada Biopharmaceutical Public

9

TT 301 Transition Therapeutics is developing TT 301, a

small molecule compound that inhibits the

overproduction of inflammatory cytokines, such

as interleukin-1 beta and tumour necrosis factor

alpha, for the treatment of central nervous

system indications such as intracerebral

haemorrhage and traumatic brain injury. [CONT.]

TT301 Cytokine inhibitors

8

NSI 189 Neuralstem is developing NSI 189, an orally

active, first-in-class, small molecule neurogenic

therapeutic for the treatment of major depressive

disorder. The compound can cross the blood-

brain barrier and appears to have the effect of

stimulating neurogenesis in the hippocampus by

"recruiting" the patient's own neural stem cells to

repair or protect against CNS damage. [CONT.]

Neurogenesis stimulants

7

Neurological disorder stem cell

therapies - Neuralstem

Neuralstem is developing neural stem cells from

the human brain and spinal cord for the

treatment of a range of neurological disorders,

including amyotrophic lateral sclerosis (ALS),

Huntington's disease, ischaemic spastic

paraplegia, stroke and traumatic spinal cord

injuries. The company's patent-protected

technology is used to control the differentiation

of the stem cells into mature physiologically

relevant human neurons and glia, and to produce

commercial quantities of these cells [CONT.]

Cell replacements

6

Zinc monocysteine Synthetic Biologics (formerly Adeona

Pharmaceuticals) is developing zinc-based

therapeutics, including a proprietary formulation

of orally available zinc monocysteine, for the

treatment of Alzheimer's disease and

amyotrophic lateral sclerosis (ALS). The product

was originally developed as a prescription

medical food; however, following positive results

from a 42 patient clinical study, the company

now plans to develop the product as a

prescription pharmaceutical [CONT.]

5

RNS 60 RNS 60 is a charge-stabilised nanostructure

(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

molecular scaffolding that could alter whole cell

conductance through effects on voltage-gated ion

channels and other voltage-sensing proteins, and

thereby modulating the expression of G-protein

coupled receptors and secretion of cytokines,

chemokines and adhesion molecules [CONT.]

4

Gene therapies - ReGenX Biosciences ReGenX Biosciences is developing personalised

gene therapies for eye, neurodegenerative,

haematological and metabolic disorders, using its

NAV™ gene delivery technology. NAV™ includes

a range of proprietary recombinant adeno-

associated viral (rAAV) vectors, including rAAV7,

rAAV8, rAAV9 and rAAVrh10. [CONT.]

NAV™ therapeutics - ReGenX Biosciences Gene transference

3

Adult neural stem cell therapy -

StemCells

StemCells is developing an adult neural stem cell

therapy, known as HuCNS-SC®, for the

treatment of disorders in all three regions of the

CNS (brain, spinal cord, eyes). Researchers at

StemCells have succeeded in purifying stem cells

away from other cells in brain tissue by using

specific stem cell markers combined with state-of-

the-art cell sorting. [CONT.]

Cell replacements

2

Stem cell therapies - RNL BIO RNL BIO (South Korea) is researching and

developing stem cell therapies derived from adult

sources, such as cord blood, placenta, hair

follicle and adipose (fat) tissue. The company is

focussing on the development of mesenchymal

stem cell therapies derived from adipose fat.

Clinical development is underway in

osteonecrosis, interverterbral disc degeneration,

osteoarthritis, thromboangiitis obliterans, facial

hemiatrophy, liver disorders, and spinal cord

injury [CONT.]

Cell replacements

Drug Development Phase Organisations

1

IRX 4204 IRX 4204 is an orally bioavailable, first in class,

retinoid X receptor (RXR; rexinoid) agonist being

developed by Io Therapeutics. The initial focus is

for the treatment of castration-resistant prostate

cancer, but may also be developed for non-small

cell lung cancer. IRX 4204 demonstrated activity

against a variety of human cancers in vitro and

in animal models, including prostate, breast,

pancreatic, and lung [CONT.]

Retinoid X receptor agonists

Alzheimer's Disease (Preclinical & Research)

Drug Introduction Synonyms Mechanism Of Action

Neuropathic pain (In volunteers) Phase I PO USA Virobay Originator USA Pharmaceutical Private

Alzheimer's disease Research PO USA Virobay Owner USA Pharmaceutical Private

VBY 106 Cathepsin B inhibitors Autoimmune disorders 0 PO USA Virobay Originator USA Pharmaceutical Private

VBY 285 Cathepsin inhibitors Bone cancer 0 Unknown route USA Virobay Owner USA Pharmaceutical Private

VBY 825 Cathepsin S inhibitors Neuropathic pain 0 PO USA

VBY-106 Hepatitis C protease inhibitors Alzheimer's disease Research PO USA

VBY-285 Cancer pain Discontinued(Preclinical) PO USA

VBY-825 Hepatitis C Discontinued(Preclinical) PO USA

AZD-3102 Alzheimer's disease Preclinical Parenteral Europe, USA AstraZeneca Licensee World Large Pharma, Pharmaceutical Public

AZD3102 Dyax Originator USA Biopharmaceutical Public

Dyax Owner USA Biopharmaceutical Public

AZD-6319 Alzheimer's disease Preclinical IM USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

AZD6319 AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

ReXceptor is developing bexarotene as a

treatment for Alzheimer's disease (AD).

Preclinical development is underway in the US.

Peroxisome proliferator-activated receptor

agonists

Alzheimer's disease Preclinical PO USA Alzheimers Drug Discovery Foundation Funder USA Company

The drug was originated by Ligand

Pharmaceuticals and is available in both oral and

topical formulations for the treatment of

cutaneous T-cell lymphoma in the US, Europe,

Bolivia and Chile [see separate profiles]. [CONT.]

Protein synthesis inhibitors BrightFocus Foundation Funder USA Investor

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

Alzheimer's disease Preclinical PO Italy Lay Line Genomics Market Licensee World Biopharmaceutical Private

University of Bologna Originator Italy University N/A

University of Bologna Owner Italy University N/A

Alzheimer's disease (Adjunctive treatment:Adjunct to

donepezil)

Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Merck & Co Owner USA Large Pharma, Pharmaceutical Public

NC-1900 Alzheimer's disease Preclinical Injection Japan Nippon Chemiphar Originator Japan Pharmaceutical Public

NC1900 Alzheimer's disease Preclinical Inhalation USA Nippon Chemiphar Owner Japan Pharmaceutical Public

Schizophrenia Preclinical Injection Japan

NXD 1191, a spheron targeting agent, is

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

with Alzheimer's disease (AD).

NXD-1191 Alzheimer's disease Preclinical Unknown route Canada Nymox Pharmaceutical Corporation Originator Canada Biopharmaceutical Public

Spherons, a brain entity discovered by Nymox

researchers, are tiny balls of densely packed

protein found in brain cells. [CONT.]

Spheron targeting drug Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public

NXD 3109, a spheron targeting agent, is in

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

Alzheimer's disease (AD).


Spherons, a brain entity discovered by Nymox

researchers, are tiny balls of densely packed

protein found in brain cells. [CONT.]

Spheron targeting agents Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public


NXD9062 Nymox Pharmaceutical Corporation Owner Canada Biopharmaceutical Public

DWJ301 Acetylcholinesterase inhibitors Alzheimer's disease Preclinical PO South Korea Cenomed BioSciences Sub-licensee World Biopharmaceutical Private

Phenserine tartrate Amyloid beta-protein precursor inhibitors Poisoning Preclinical PO USA Daewoong Pharmaceutical Sub-licensee South Korea Pharmaceutical Public

Alzheimer's disease Discontinued(Clinical) PO USA National Institute on Aging Originator USA Institution N/A

Cognition disorders Discontinued PO USA National Institutes of Health (USA) Originator USA Institution N/A

QR Pharma Sub-licensee World Biotechnology

Raptor Pharmaceutical Corp Licensee World Pharmaceutical Public

Alzheimer's disease Preclinical Unknown route South Korea Medifron DBT Originator South Korea Technology provider Public

21

Phenserine Phenserine is a phenylcarbamate analogue of

physostigmine and a selective

acetylcholinesterase inhibitor that is being

developed for the teatment of poisoning following

exposure to organophosphorous nerve agents

and Alzheimer's disease (AD). The compound

was discovered by the National Institute on Aging

(NIA) of the US National Institutes of Health

(NIH). [CONT.]

22

Research programme: advanced

glycosylation end product receptor

antagonists - Medifron

Medifron DBT is developing advanced

glycosylation end-product receptor antagonists

for the treatment of Alzheimer's disease. The

efficacy of lead candidates have been proven in a

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.]

Advanced glycosylation end-product receptor

antagonists

19

NXD 3109

20

NXD 9062 Nymox Pharmaceutical Corporation is

preclinically developing NXD 9062 as a potential

treatment for Alzheimer's disease (AD) in

Canada. NXD 9062 works by inhibiting cell

damage similar to that found in the AD brain. The

agent is undergoing further preclinical

development in Canada.

Undefined mechanism

17

NC 1900 Japan-based pharmaceutical company Nippon-

Chemiphar is developing the active-fragment

analogue of arginine-vasopressin, NC 1900, for

the potential treatment of Alzheimer's disease.

The drug has also been investigated in a

preclinical model of schizophrenia. [CONT.]

Undefined mechanism

18

NXD 1191

Undefined mechanism

16

MK 7622 Merck is developing MK 7622, a small-molecule

quinazolinone compound, as a potential therapy

for Alzheimer's disease (AD). A phase IIb trial

(MK-7622-012 AM1) is planned in the US to

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

(NCT01852110). [CONT.]

MK-7622

14

Bexarotene - ReXceptor

15

Memoquin Lay Line Genomics is developing memoquin, a

low molecular weight molecule based on a

chemical scaffold able to support multiple

pharmacophores, as a potential therapeutic for

Alzheimer's disease. It has been developed with

the aim of obtaining a multifunctional molecule

effective on different biochemical cascades,

relevant for Alzheimer's-like pathology. [CONT.]

12

AZD 3102 AZD 3102 is a human monoclonal antibody with

high affinity for an undisclosed Alzheimer's

disease (AD) target. The antibody is being

developed by AstraZeneca in collaboration with

Dyax, and could have utility in the modification of

AD progression. Preclinical development is

underway in the US and Europe.

Undefined mechanism

13

AZD 6319 AstraZeneca is developing AZD 6319, a selective

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

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.]

Nicotinic receptor agonists

11

Research programme: protease

inhibitors - Virobay

Virobay in the US has a research programme

developing small-molecule protease inhibitors for

the treatment of Alzheimer's disease,

autoimmune diseases, bone cancer, hepatic

fibrosis, neuropathic pain and cancer. The

company has developed HCV protease inhibitors

and cathepsin inhibitors. Development has

reached phase 0 development in autoimmune

disorders, bone cancer and neuropathic pain, and

early research is being conducted in Alzheimer's

disease [CONT.]

10

VBY 036 Virobay is developing a selective small-molecule

cathepsin S inhibitor, VBY 036, as an oral

treatment for neuropathic pain and Alzheimer's

disease. ViroBay proposes that the drug is first-in-

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.]

VBY-036 Cathepsin S inhibitors

Medifron DBT Owner South Korea Technology provider Public

A2A PAM Adenosine A2 receptor modulators Alcoholism Preclinical PO Switzerland Addex Pharmaceuticals Originator Switzerland Pharmaceutical Public

ADX 68692 Follicle stimulating hormone modulators Alzheimer's disease Preclinical PO Switzerland Addex Therapeutics Owner Switzerland Pharmaceutical Public

ADX 71441 GABA B receptor agonists Charcot-Marie-Tooth disease Preclinical PO Germany, Netherlands Viva Biotech Collaborator China CRO Private

ADX 71743 Interleukin 2 receptor modulators Endometriosis Preclinical PO Switzerland

ADX 71943 Interleukin-1 receptor modulators Gastro-oesophageal reflux Preclinical PO Switzerland

ADX 92639 Metabotropic glutamate receptor 2 modulators Major depressive disorder Preclinical PO Switzerland

ADX-71743 Metabotropic glutamate receptor 7 modulators Muscle spasticity Preclinical PO Switzerland

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

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

tumours and reproductive system disorders -

Addex Therapeutics

Osteoarthritis Research PO Switzerland

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

EVP 4473 Alzheimer's disease Preclinical PO USA Bayer HealthCare Originator Germany Pharmaceutical Public

EVP-4473 Schizophrenia Preclinical PO USA Bayer HealthCare Pharmaceuticals Owner Germany Pharmaceutical Public

EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private

alpha7 nAChR agonists - Memory

Pharmaceuticals/Roche

Alpha7 nicotinic acetylcholine receptor agonists Alzheimer's disease Preclinical PO USA Memory Pharmaceuticals Originator USA Biopharmaceutical Public

Nicotinic alpha-7 receptor agonists - Memory

Pharmaceuticals/Roche

Nicotinic receptor agonists Schizophrenia Preclinical PO USA Memory Pharmaceuticals Owner USA Biopharmaceutical Public

BNC 1881 Alzheimer's disease Preclinical Unknown route Australia Bionomics Originator Australia Biotechnology Public

BNC 375 Cognition disorders Preclinical Unknown route Australia Bionomics Owner Australia Biotechnology Public

BNC1881

BNC375

Alzheimer's disease (Diagnosis) Preclinical Unknown route Singapore Bayer HealthCare Pharmaceuticals Owner Germany Pharmaceutical Public

Parkinson's disease (Diagnosis) Preclinical Unknown route Singapore Bayer Schering Pharma Originator Germany Pharmaceutical Public

WisTa Laboratories Originator Singapore Pharmaceutical Private

WisTa Laboratories Owner Singapore Pharmaceutical Private

INVENT Pharmaceuticals is developing small

molecule therapeutics for the treatment of

Alzheimer's disease and age-related cognitive

and memory impairment. The company utilises

its proprietary site-specific drug design and

discovery platform for creation of new

candidates.

Alzheimer's disease Preclinical Unknown route USA INVENT Pharmaceuticals Originator USA Biotechnology Private

INVENT is actively seeking partners for potential

drug discovery, and drug development and

commercialisation collaborations.

Cognition disorders Preclinical Unknown route USA INVENT Pharmaceuticals Owner USA Biotechnology Private

Memory disorders Preclinical Unknown route USA

Alzheimer's disease (Diagnosis) Preclinical Unknown route USA Avid Radiopharmaceuticals Originator USA Technology provider Public

Avid Radiopharmaceuticals Owner USA Technology provider Public

Siemens Medical Solutions Originator USA Technology provider Public

Alzheimer's disease (Diagnosis) Preclinical Unknown route USA Blanchette Rockefeller Neurosciences Institute Originator USA Institution N/A

Alzheimer's disease Preclinical Unknown route USA Neurotrope BioScience Originator USA Biotechnology

Anti-Abeta oligomers - LLG Amyloid beta-protein inhibitors Alzheimer's disease (Diagnosis) Preclinical Unknown route Italy Lay Line Genomics Originator Italy Biopharmaceutical Private

Anti-beta-amyloid oligomers - LLG Nerve growth factor stimulants Alzheimer's disease Preclinical Unknown route Italy Lay Line Genomics Owner Italy Biopharmaceutical Private

Anti-proNerve Growth Factor - LLG

Anti-proNGF - LLG

Diagnostic antibody IM13 - LLG

NGF-based therapy - LLG

Alzheimer's disease Preclinical Unknown route USA Nuron Biotech Licensee World Biotechnology Private

University of Texas Southwestern Medical Center Originator USA University N/A

VITRUVIAN BioMedical Owner USA Biotechnology

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Israel NasVax Originator Israel Biopharmaceutical Public

33

Research programme: Alzheimer's

disease immunotherapeutics -

NasVax

NasVax in Israel is developing

immunotherapeutic products for Alzheimer's

disease. The company is developing two products

based on BBS technology. The two products are

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.]

32


disease DNA vaccine - VITRUVIAN

BioMedical/Nuron Biotech

VITRUVIAN BioMedical is developing a DNA

amyloid beta 42 (Abeta42) vaccine for treatment

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

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

Abeta are produced [CONT.]

Amyloid beta 42 DNA vaccine for Alzheimer's

disease - Nuron Biotech

Immunostimulants

30


disease diagnostics and therapeutics -

Blanchette Rockefeller

Neurosciences Institute/Neurotrope

BioScience

The Blanchette Rockefeller Neurosciences

Institute (BRNI) and Neurotrope BioScience are

collaborating to develop and commercialise

diagnostic and therapeutic agents for Alzheimer's

disease. Development is at the preclinical stage

in the US.

31


disease diagnostics and therapies -

Lay Line Genomics

Lay Line Genomics is researching several

products for use as diagnostics and/or therapies

for Alzheimer's disease. Preclinical development

is underway in Italy.

28


disease and cognition disorder

therapeutics - INVENT

Pharmaceuticals

Undefined mechanism

29


disease diagnostics - Avid

Radiopharmaceuticals

Avid Radiopharmaceuticals, a molecular imaging

subsidiary of Eli Lilly, is developing positron

emission tomography (PET) tracers for the

diagnosis of Alzheimers disease (AD). AD

hallmarks such as cognitive impairment and

neuronal circuit degeneration can be correlated

with the severity of tau abnormalities and

neurofibrillary tangles (NFT) burden. [CONT.]

Tau tangle diagnostic program Positron-emission tomography enhancers

27


and Parkinson's disease diagnostic

agents - Bayer HealthCare

Pharmaceuticals/TauRx

WisTa Laboratories Ltd., a wholly owned

subsidiary of TauRx Pharmaceuticals, is

collaborating with Bayer HealthCare

Pharmaceuticals (formerly Bayer Schering

Pharma) in the development of specific markers

that will aid in the diagnosis and management of

Tau-protein related Alzheimer's disease (AD),

using brain-imaging technology. The programme

may also have potential in the development of

diagnostics for Parkinson's disease [CONT.]

26

Research programme: alpha7

nicotinic acetylcholine receptor

modulator therapeutics - Bionomics

Bionomics is developing positive allosteric

modulators (PAMs) of the alpha7 nicotinic

acetylcholine receptor (nAChR) for the treatment

of Alzheimer's disease and cognitive impairment

related to conditions such as attention deficit

hyperactivity disorder (ADHD), mood and anxiety

disorders, multiple sclerosis, Parkinson's disease,

and schizophrenia. [CONT.]

Alpha7 nicotinic acetylcholine receptor

modulators

25

Research programme: alpha-7


agonists - Roche

Roche are developing orally active, nicotinic

alpha-7 (alpha7) receptor agonists for the

treatment of various central nervous system

disorders (CNS), particularly Alzheimer's disease

(AD) and cognitive impairment associated with

schizophrenia (CIAS). The nicotinic alpha7

receptor acts to promote neuronal function,

acting on synaptic plasticity and cytoprotection.

[CONT.]

24

Research programme: alpha-7


agonists - EnVivo Pharmaceuticals

EnVivo Pharmaceuticals is developing selective,

orally active alpha-7 nicotinic acetylcholine

receptor (alpha7-nAChR) agonists for the

treatment of cognitive decline in patients with

Alzheimer's disease (AD) and schizophrenia. The

rationale behind selective activation of alpha7-

nAChRs is to enhance cognition without causing

the adverse events associated with

overactivation of other nAChRs or muscarinic

acetylcholine receptors [CONT.]

Alpha7 nicotinic acetylcholine receptor agonists

23

Research programme: allosteric

modulators - Addex Therapeutics

Positive and negative allosteric modulators are

being developed by Addex Therapeutics (formerly

Addex Pharmaceuticals) for the treatment of a

variety of diseases. The compounds are orally

available small molecules that have potential use

in overactive bladder, gastro-oesophageal reflux

disease (GERD), endometriosis, pain, urinary

incontinence, glaucoma, depression, anxiety,

Alzheimer's disease, type [CONT.]

22

Research programme: advanced

glycosylation end product receptor

antagonists - Medifron

Medifron DBT is developing advanced

glycosylation end-product receptor antagonists


efficacy of lead candidates have been proven in a

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.]


antagonists

Immunostimulants NasVax Owner Israel Biopharmaceutical Public

anti-ADDL antibodies Alzheimer's disease Preclinical Injection USA Acumen Pharmaceuticals Licensee USA Biotechnology

HuC 091 Northwestern University Originator USA University N/A

HuC091 Northwestern University Owner USA University N/A

Alzheimer's disease Preclinical Parenteral Australia Prana Biotechnology Originator Australia Biotechnology Public

Prana Biotechnology Owner Australia Biotechnology Public

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Finland Medeia Therapeutics Originator Finland Pharmaceutical Private

Cell replacements Medeia Therapeutics Owner Finland Pharmaceutical Private

Alzheimer's disease Preclinical PO Japan Institute of Medicinal Molecular Design Originator Japan Pharmaceutical Private

Institute of Medicinal Molecular Design Owner Japan Pharmaceutical Private

ACI-518 Alzheimer's disease Preclinical Unknown route Switzerland AC Immune Originator Switzerland Biotechnology Private

ACI-636 AC Immune Owner Switzerland Biotechnology Private

Alzheimer's disease Preclinical Unknown route USA AgeneBio Originator USA Pharmaceutical Private

Mild cognitive impairment Preclinical Unknown route USA AgeneBio Owner USA Pharmaceutical Private

Amgen Inc is developing orally available small

molecule BACE (beta-site APP-cleaving enzyme)

inhibitors for the treatment of Alzheimer's

disease. Preclinical development is ongoing in the

US.

AMG-0683 Alzheimer's disease Preclinical PO USA Amgen Originator USA Large Pharma, Biotechnology Public

Cerebral deposition of amyloid beta peptide

(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.]

AMG0683 Amgen Owner USA Large Pharma, Biotechnology Public

CMP 015

Alzheimer's disease Preclinical Unknown route USA Applied NeuroSolutions Originator USA Biopharmaceutical Public

Applied NeuroSolutions Owner USA Biopharmaceutical Public

Eli Lilly Licensee World Large Pharma, Pharmaceutical Public

ARC 050 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical Unknown route USA Archer Pharmaceuticals Originator USA Pharmaceutical Private

ARC 069 Calcium channel antagonists Archer Pharmaceuticals Owner USA Pharmaceutical Private

ARC050

ARC069

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route Switzerland Merck Serono Originator Switzerland Biopharmaceutical Public

Tau protein inhibitors Merck Serono Owner Switzerland Biopharmaceutical Public

Alzheimer's disease Preclinical Unknown route Austria, Germany Boehringer Ingelheim Licensee Germany Large Pharma, Pharmaceutical Private

Evotec AG Originator Germany Pharmaceutical Public

Evotec AG Owner Germany Pharmaceutical Public

Research Institute of Molecular Pathology Collaborator Austria Institution N/A

Abeta oligomerisation inhibitors Alzheimer's disease Preclinical Intracerebro ventricular United Kingdom BTG Originator United Kingdom Pharmaceutical Public

Amyloid-beta oligomerisation inhibitors BTG Owner United Kingdom Pharmaceutical Public

BGC 200406 Senexis Licensee World Company

44


disease therapeutics - Boehringer

Ingleheim/Evotec AG

Evotech and Boehringer Ingleheim are

collaboratively investigating potential points of

intervention in the treatment of Alzheimer's

disease. Evotec utilises a Fragment Based Drug

Discovery (FBDD) and screening platform to

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

identify lead structures and preclinical

development candidates [CONT.]

BACE1 protein inhibitors

45


disease therapeutics - BTG/Senexis

Senexis is investigating small molecule, peptide-

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

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.]

Amyloid beta-protein inhibitors

42


disease therapeutics - Archer

Pharmaceuticals

Archer Pharmaceuticals, a spin-off company of

The Roskamp Institute, is developing compounds

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

The Roskamp Institute is devoted to

understanding causes and finding cures for

neuropsychiatric and neurodegenerative

disorders and addictions. Archer Pharmaceuticals

aims to find existing drugs that can be

repositioned into AD therapies and to use these

drugs as templates for the development of new,

more effective drugs. [CONT.]

43


disease therapeutics - Asceneuron

Asceneuron (a Merck Serono spin-off company)

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

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.]

40


disease therapeutics - Amgen


41


disease therapeutics - Applied

NeuroSolutions/Eli Lilly

Applied NeuroSolutions (formerly Molecular

Geriatrics Corporation), in collaboration with Eli

Lilly, is using in vitro screens in a combinatorial

chemistry programme that aims to discover

novel therapeutics for the treatment of

Alzheimer's disease (AD). Development is at the

research stage in the US. [CONT.]

Undefined mechanism

Plasminogen activator inhibitor-1 inhibitors

38


disease therapeutics - AC Immune

AC Immune has a research programme

investigating therapeutics for the treatment of

Alzheimer's disease. The programme is

investigating Morphomers™ which are non-

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.]

39


disease therapeutics - AgeneBio

AgeneBio is developing small-molecule

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

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.]

GABA modulators

36


disease stem cell therapy - Medeia

Therapeutics

Medeia Therapeutics is developing MDA 208C, a

stem cell therapy for the treatment of

Alzheimer's disease (AD). The company is using

its MDA 200C cell-based therapy platform

involving stem cells derived from bone marrow.

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.]

MDA-208C

37


disease therapeutic - Institute of

Medicinal Molecular Design

The Institute of Medicinal Molecular Design, Inc.

(IMMD) is developing IMD 4690, an orally

administered inhibitor of PAI-1 (plasminogen

activator inhibitor-1), for the treatment of

Alzheimer's disease. IMD 4690 is undergoing

preclinical development in Japan.

IMD-4690


35


disease immunotherapy - Prana

Biotechnology

Prana Biotechnology is developing an

immunotherapy for Alzheimer's disease. The

research is assessing the effectiveness of the

technology to enhance the production of

antibodies as an effective Alzheimer's disease

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

disease [CONT.]

4,00E+10 Immunostimulants

33


disease immunotherapeutics -

NasVax

NasVax in Israel is developing

immunotherapeutic products for Alzheimer's

disease. The company is developing two products

based on BBS technology. The two products are

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.]

34


disease immunotherapy -

Acumen/Merck

Acumen Pharmaceuticals is developing

immunotherapies against amyloid beta-derived

diffusible ligand (ADDL). ADDLs are highly

ordered aggregates of amyloid beta1-42

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

in patients with memory-related disorders.

[CONT.]

BGC 200466

BGC 201178

RS 0406

RS 0466

RS 1178

SEN 1269

SEN-1269

SEN1269

haw AD14 Alzheimer's disease Preclinical PO USA CoPlex Therapeutics Originator USA Pharmaceutical Private

hawAD14 CoPlex Therapeutics Owner USA Pharmaceutical Private

Hawthorn Pharmaceuticals Licensee World Pharmaceutical Private

DWJ 501 Alzheimer's disease Preclinical PO South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public

DWJ501 Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public

FGL-S Alzheimer's disease Preclinical Parenteral Denmark ENKAM Pharmaceuticals A/S Originator Denmark Biotechnology Private

FGLS Cognition disorders Preclinical Parenteral Denmark ENKAM Pharmaceuticals A/S Owner Denmark Biotechnology Private

Forenap Collaborator France CRO Private

Lundbeck A/S Collaborator Denmark Large Pharma, Pharmaceutical Public

Prague Psychiatric Center Collaborator Czech Republic Institution N/A

Qualissima Collaborator France CRO Private

University Hospital of Cologne Collaborator Germany Hospital N/A

University of Copenhagen Collaborator Denmark University N/A

KaloBios Pharmaceuticals is investigating an

antibody to granulocyte macrophage colony-

stimulating factor (GM-CSF) as a potential

therapy for Alzheimer's disease. Preclinical

studies are in progress in the US.

Alzheimer's disease Preclinical Parenteral USA KaloBios Pharmaceuticals Originator USA Biopharmaceutical Private

Analysis of brain tissue from patients with

Alzheimer's disease has revealed the presence of

inflammation caused by proliferation of microglia

and astrocytes. [CONT.]

KaloBios Pharmaceuticals Owner USA Biopharmaceutical Private

Alzheimer's disease Preclinical Unknown route Switzerland Kareus Therapeutics Originator Switzerland Pharmaceutical Private

Kareus Therapeutics Owner Switzerland Pharmaceutical Private

Alzheimer's disease Preclinical Unknown route USA Medisyn Technologies Originator USA Biotechnology

Mount Sinai School of Medicine Originator USA University N/A

Alzheimer's disease Preclinical Unknown route Germany, Israel Merz Pharmaceuticals GmbH Originator Germany Pharmaceutical Private

Merz Pharmaceuticals GmbH Owner Germany Pharmaceutical Private

Ramot at Tel Aviv University Technology Transfer Israel Technology Transfer Private

Tel Aviv University Collaborator Israel University N/A

Tel Aviv University Technology Provider Israel University N/A

Alzheimer's disease Preclinical Unknown route USA Mithridion Licensee World Biopharmaceutical

University of Wisconsin System Originator USA University N/A

University of Wisconsin System Owner USA University N/A

Wisconsin Alumni Research Foundation Technology Transfer World Technology Transfer Private

Neu AZ1 Alzheimer's disease Preclinical Unknown route Israel Neurim Pharmaceuticals Originator Israel Pharmaceutical Private

Neu-AZ1 Neurim Pharmaceuticals Owner Israel Pharmaceutical Private

NeuAZ1

2 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Neuro-Hitech Originator USA Pharmaceutical Public

3 Tau protein inhibitors Neuro-Hitech Owner USA Pharmaceutical Public

4-Trihydroxybenzophenone

4-Amino 1

1'-azobenzene-3

4'-disulfonic acid sodium salt

Pain Therapeutics is developing orally available,

small molecule compounds for the treatment of

Alzheimer's disease. A lead candidate from this

programme, known as PTI 125, is in preclinical

development in the US.

PTI 125 Alzheimer's disease Preclinical PO USA Pain Therapeutics Originator USA Biopharmaceutical Public

PTI 125 binds with high affinity to filamin A

(FLNA), a microfilament scaffolding protein which

has been shown to play an important role in

amyloid-beta42 signalling. [CONT.]

PTI-125 Pain Therapeutics Owner USA Biopharmaceutical Public

Roche is developing inhibitors of beta-secretase

(BACE-1), for the treatment of Alzheimer's

disease (AD). The programme is undergoing

preclinical development in Switzerland.

R 641 Alzheimer's disease Preclinical Unknown route Switzerland Roche Originator Switzerland Large Pharma, Pharmaceutical Public

The accumulation of amyloid beta-peptide

(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.]

R-641 Roche Owner Switzerland Large Pharma, Pharmaceutical Public

56


disease therapeutics - Pain

Therapeutics

Microfilament protein inhibitors

57


disease therapeutics - Roche


54


disease therapeutics - Neurim

Pharmaceuticals

Neurim Pharmaceuticals is developing

compounds for the treatment of Alzheimer's

disease. The mechanism of action is undisclosed.

The company has identified Neu AZ1 as a lead

candidate, and is in preclinical development,

presumably in Israel.

Undefined mechanism

55


disease therapeutics - Neuro-Hitech

Neuro-Hitech (formerly Q-RNA) is developing

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

of Abeta plaques and the intraneuronal

accumulation of hyperphosphorylated tau protein

as neurofibrillary tangles are implicated in the

pathogenesis of AD. Development is at the

preclinical stage in the US. [CONT.]

52


disease therapeutics - Merz

Pharmaceuticals/Tel Aviv University

Merz Pharmaceuticals and Tel Aviv University are

collaborating in a research programme to

develop and commercialise therapeutics for

Alzheimer's disease. Both parties will jointly

evaluate candidate compounds identified using

the University's proprietary drug discovery

technology. The programme is being conducted

in Germany and Israel.

Undefined mechanism

53


disease therapeutics - Mithridion

Mithridion is undertaking a research programme

to develop next-generation, disease-modifying


disease (AD). Such small molecule drugs are

intended to delay or halt AD progression,

particularly the degeneration and death of

neurons via inhibition of amyloid-beta (Abeta).

This approach is expected to preserve memory,

cognitive and other brain functions. [CONT.]


51


disease therapeutics - Medisyn

Medisyn and the Mount Sinai School of Medicine

are developing therapeutics for the treatment of

Alzheimer's disease. Using Medisyn's Forward

Engineering™ technology, eight lead compounds

have been discovered with significant in vitro

activity, two have also been tested in vivo with

promising results. [CONT.]


49


disease therapeutics - KaloBios

Pharmaceuticals

Granulocyte macrophage colony stimulating

factor antagonists

50


disease therapeutics - Kareus

Therapeutics

Kareus Therapeutics is developing compounds for

the treatment of Alzheimer's disease. The

company aims to create therapeutics that

intervene in the disease causing mechanism, to

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.]

DMAD Amyloidogenic protein inhibitors

47


disease therapeutics - Daewoong

Pharmaceutical

Daewoong Pharmaceutical is developing oral


disease. DWJ 501, a lead candidate from the

programme, is a herbal extract. Daewoong is

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.]

Undefined mechanism

48


disease therapeutics - ENKAM

ENKAM Pharmaceuticals is developing a peptide

compound, FGLS, for the treatment of

Alzheimer's disease and potentially other

conditions that feature impaired cognition, such

as Parkinson's disease and stroke. FGLS is one of

a family of compounds known as FGL (or FGL

peptides) that function as allosteric fibroblast

growth factor receptor modulators. [CONT.]

Fibroblast growth factor receptor modulators

46


disease therapeutics - CoPlex

Therapeutics/Hawthorn

Pharmaceuticals

Hawthorn is developing haw AD14, an orally-

administered small molecule originated by CoPlex

Therapeutics, which may have potential in the

treatment of Alzheimer's disease. The compound

has been shown to significantly decrease levels

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

Alzheimer's disease [CONT.]

45


disease therapeutics - BTG/Senexis

Senexis is investigating small molecule, peptide-


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

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.]


Alzheimer's disease Preclinical Unknown route Switzerland Roche Originator Switzerland Large Pharma, Pharmaceutical Public

Neurodegenerative disorders Preclinical Unknown route Italy Siena Biotech Originator Italy Company

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Senex Biotechnology Originator USA Biotechnology Private

Amyloid beta-protein precursor inhibitors Senex Biotechnology Owner USA Biotechnology Private


Signal transduction pathway inhibitors

Transglutaminase inhibitors

SEN1176 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route USA Senexis Originator United Kingdom Company

SEN1500 Macrophage inhibitors Senexis Owner United Kingdom Company

SEN1576

SEN304

SEN606

M007 LRPIV Alzheimer's disease Preclinical Unknown route USA Socratech Originator USA Biotechnology Private

M007-LRPIV Socratech Owner USA Biotechnology Private

Alzheimer's disease Preclinical Unknown route USA Sonexa Therapeutics Licensee World Biopharmaceutical Private

Unknown Originator USA Company

Unknown Owner USA Company

ANA-1 Amyloid beta-protein inhibitors Alzheimer's disease (Diagnosis) Preclinical PO Australia Alzhyme Originator Australia Biopharmaceutical Private

ANA-5 Superoxide dismutase inhibitors Alzheimer's disease Preclinical PO Australia Alzhyme Owner Australia Biopharmaceutical Private

ANSTO Radiopharmaceuticals and Industrials Collaborator Australia Company

CSIRO Collaborator Australia Agency

Alzheimer's disease Preclinical PO United Kingdom Galapagos NV Originator Belgium Pharmaceutical Public

Senexis Originator United Kingdom Company

Biogen Idec is developing therapies for

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

precursor protein secretase modulator).

Alzheimer's disease Preclinical Unknown route Unknown Biogen Idec Originator USA Large Pharma, Biotechnology Public

The neurodegeneration observed in AD is thought

to be a result of a pathological cascade initiated

by formation of insoluble plaques caused by the

accumulation of amyloid beta (Abeta) peptides

[CONT.]

Biogen Idec Owner USA Large Pharma, Biotechnology Public

Amyloid precursor protein secretase modulators Alzheimer's disease Preclinical PO USA Cellzome Originator Germany Pharmaceutical Private

Tau protein modulators Johnson & Johnson Pharmaceutical Research &

Development

Originator USA Pharmaceutical Public

Mazal Plant Pharmaceuticals, a majority owned

subsidiary of Adavanced Plant Pharmaceuticals,

is developing MAALZ [LMH 123] for the

treatment of leukaemia. MAALZ is a plant based

composition. Preclinical trials with the compound

are ongoing in the US.

LMH-123 Alzheimer's disease Preclinical Unknown route USA Mazal Plant Pharmaceuticals Originator USA Company

MAALZ was originally developed by Advanced

Plant Pharmaceuticals Inc (APPI). [CONT.]

MAALZ Mazal Plant Pharmaceuticals Owner USA Company

SEN 12333 Alzheimer's disease Preclinical Unknown route Italy Siena Biotech Originator Italy Company

SEN 34625 Siena Biotech Owner Italy Company

SEN34625

WAY-317538

WYE 103914

WYE-103914

Alzheimer's disease therapy research programme

- Satori Pharmaceuticals

Alzheimer's disease Preclinical Unknown route USA Satori Pharmaceuticals Originator USA Company

69


disease therapy - Satori

Pharmaceuticals

Satori Pharmaceuticals is developing gamma-

secretase modulators as a disease modifying

therapy for Alzheimer's disease (AD). AD is

characterized by the formation of amyloid beta

(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.]

Amyloid precursor protein secretase modulators

67


disease therapies - Mazal Plant

Pharmaceuticals

Undefined mechanism

68


disease therapies - Siena Biotech

Siena Biotech is developing compounds for the

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

targets. These receptors are expressed in brain

regions associated with cognitive function,

regulate cholinergic neurotransmission and have

been shown to be down-regulated in Alzheimer's

disease. Development is at the preclinical stage.

[CONT.]

Alpha7 nicotinic acetylcholine receptor agonists

65


disease therapies - Biogen Idec

Gamma secretase modulator - Biogen Idec Amyloid precursor protein secretase modulators

66


disease therapies - Cellzome/Ortho-

McNeil Pharmaceutical

Cellzome Inc., and Johnson & Johnson

Pharmaceutical Research & Development in the

US are collaborating in a research programme

focused on identifying orally administered,

amyloid precursor protein secretase (gamma-

secretase) modulators and tau protein

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

new drug targets [CONT.]

63


disease therapies - Alzhyme

Alzhyme, an Australian biotechnology company,

is developing orally available, peptide analogues


company has identified two peptides, ANA-1 and

ANA-5, which bind to human beta-amyloid

(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-

amyloid catalytic production of hydrogen

peroxide [CONT.]

64


disease therapies - BioFocus/Senexis

Galapagos (formerly BioFocus) and 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

potential treatment of Alzheimer's disease.

BioFocus' medicinal chemistry capabilities will be

used to accelerate the lead discovery of Senexis'

compounds.

beta-sheet breakers Amyloid inhibitors

61


disease therapeutics - Socratech LLC

Socratech LLC is developing therapeutics

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

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.]

Transcription factor modulators

62


disease therapeutics - Sonexa

Therapeutics

Sonexa Therapeutics is undertaking a research

programme to develop an undisclosed drug for

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

company has licensed exclusive rights worldwide

(except for Japan and certain Asian countries) to

the compound from an undisclosed Japanese

pharmaceutical company. Development is at the

preclinical stage.

Undefined mechanism

60


disease therapeutics - Senexis

Senexis is investigating peptide- and non-peptide-


toxicity and neuroinflammation for the treatment

of Alzheimer's disease (AD) and other amyloid-

associated diseases. Toxic oligomers are created

by Abeta aggregation, which is considered key to

the onset of AD. Development of peptide-based

inhibitors of amyloid aggregation is at the

preclinical stage in the UK. [CONT.]

58


disease therapeutics - Roche/Siena

Biotech

Roche and Siena Biotech are collaborating on the

development of compounds for the treatment of

neurodegenerative disorders, including

Alzheimer's disease. Preclinical development is

underway in Italy and Switzerland.

Undefined mechanism

59


disease therapeutics - Senex

Biotechnology

Senex Biotechnology is undertaking a drug

discovery programme to develop compounds for

the treatment of major age-related diseases,

particularly Alzheimer's disease (AD). The

company is developing drugs targeting signalling

pathways activated in the process of cell

senescence or aging. Studies on functional

genomics have revealed that aging cells

overproduce proteins causing AD and other age-

related diseases [CONT.]

SPI 014 Satori Pharmaceuticals Owner USA Company

SPI 1865

SPI-014

SPI-1865

Alzheimer's disease Preclinical Unknown route USA Thuris Corporation Originator USA Pharmaceutical Private

Thuris Corporation Owner USA Pharmaceutical Private

EB 101 Alzheimer's disease (Prevention) Preclinical Parenteral USA Atlas Pharmaceuticals Originator USA Pharmaceutical

EB101 Alzheimer's disease Preclinical Parenteral USA Atlas Pharmaceuticals Owner USA Pharmaceutical

Alzheimer's disease Preclinical Transmucosal Japan DNAVEC Corporation Originator Japan Technology provider Private

Eisai Co Ltd Originator Japan Large Pharma, Pharmaceutical Public

DNAVEC is co-developing a nasal spray vaccine

against Alzheimer's disease with the National

Institute for Longevity Sciences of the National

Center for Geriatrics and Gerontology in Japan.

Alzheimer's disease Preclinical Intranasal Japan DNAVEC Corporation Originator Japan Technology provider Private

The vaccine is being developed using Sendai

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.]

National Institute for Longevity Sciences Originator Japan Institution N/A

Alzheimer's disease Preclinical Parenteral Switzerland AC Immune Originator Switzerland Biotechnology Private

AC Immune Owner Switzerland Biotechnology Private

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral Austria AFFiRiS Originator Austria Biotechnology Private

Immunostimulants AFFiRiS Owner Austria Biotechnology Private

GlaxoSmithKline Licensee World Large Pharma, Pharmaceutical Public

RV 01 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral USA Intellect Neurosciences Originator USA Biopharmaceutical Public

RV 02 Immunostimulants Intellect Neurosciences Owner USA Biopharmaceutical Public

RV 03 T lymphocyte stimulants University of California at Irvine Collaborator USA University N/A

RV01 Tau protein inhibitors

RV02

RV03

Alzheimer's disease Preclinical Intraperitoneal USA Mapp Biopharmaceutical Originator USA Biopharmaceutical

Mapp Biopharmaceutical Owner USA Biopharmaceutical

Alzheimer's disease Preclinical Unknown route USA Pfizer Originator USA Large Pharma, Pharmaceutical Public

Asthma Preclinical Unknown route USA Pfizer Owner USA Large Pharma, Pharmaceutical Public

Cancer Preclinical Unknown route USA Washington University School of Medicine Collaborator USA University N/A

Diabetes mellitus Preclinical Unknown route USA

Alzheimer's disease Preclinical Unknown route USA Star Scientific Originator USA Pharmaceutical Public

Neurological disorders Preclinical Unknown route USA Star Scientific Owner USA Pharmaceutical Public

ADDL therapeutics Alzheimer's disease Preclinical Unknown route USA Acumen Pharmaceuticals Originator USA Biotechnology

anti-ADDL therapeutics Acumen Pharmaceuticals Owner USA Biotechnology

A 887755 Alzheimer's disease Preclinical Parenteral Germany, USA Abbott GmbH & Co. KG Originator Germany Pharmaceutical Public

A-887755 Abbott GmbH & Co. KG Owner Germany Pharmaceutical Public

CT 0093 Alzheimer's disease Preclinical Unknown route USA Cognition Therapeutics Originator USA Pharmaceutical Private

82

Research programme: amyloid beta-

protein inhibitors - Cognition

Therapeutics

Cognition Therapeutics is developing small

molecule, amyloid beta-protein inhibitors, as a

disease-modifying treatment for Alzheimer's

disease. The lead candidates inhibit the activity

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.]


80


derived diffusible ligand inhibitors -

Acumen

Acumen is developing small molecule


disease that target amyloid beta-derived

diffusable ligands (ADDLs). ADDLs are highly

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

and nerve cell death. [CONT.]


81


protein inhibitors - Abbott

Abbott GmbH is developing amyloid-beta (Abeta)

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

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.]


79

Research programme: amyloid beta

protein inhibitors - Star Scientific

Star Scientific, in collaboration with SRQ Bio

(Roskamp Institute), are developing an amyloid

beta protein inhibitor for the treatment of

neurological disorders, including Alzheimer's

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

US.


77


disease vaccines - MAPP

Biopharmaceutical

MAPP Biopharmaceutical is developing

monoclonal antibodies against amyloid beta-

protein (13-28) for the treatment of cognitive

deficits associated with Alzheimer's disease (AD).

Development is at preclinical stage in the US.


78


disease, cancer, metabolic disorders

and respiratory disease therapeutics -

Pfizer/Washington University

Pfizer and Washington University School of

Medicine at St. Louis have entered into a

collaboration for the discovery of new indications

for a number of Pfizer's existing compounds that

have previously undergone preclinical or clinical

testing. The identificiation of new uses for

existing compounds is known as indications

discovery. [CONT.]

76


disease vaccines - Intellect

Neurosciences

Intellect Neurosciences is developing therapeutic

approaches, including vaccines and antibodies,

for the treatment and prevention of Alzheimer's

disease (AD). The company believes that such

approaches will potentially overcome the

incidence of autoimmune reactions or other

serious adverse events, which have hampered

progress in the field of AD therapy. Development

is at the preclinical stage in the US. [CONT.]

75


disease vaccines -

AFFiRiS/GlaxoSmithKline

AFFiRiS and GlaxoSmithKline (GSK) are

collaborating in the development of vaccine

candidates for the treatment of Alzheimer's

disease. The vaccines will be customised using

AFFiRiS' Affitope platform technology (Affitom®)

and are designed to induce cross-reactive

antibodies against a native antigen, without

producing a systemic immune response. [CONT.]

73


disease vaccine intranasal - DNAVEC

Alzheimer's disease vaccine intranasal research

programme - DNAVEC

Immunostimulants

74


disease vaccines - AC Immune

AC Immune is developing new therapies for the

treatment of Alzheimer's disease, using

vaccination or passive immunisation with

antibodies. The company has two programmes

investigating immunotherapies targeting two

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.]

Alzheimer's disease vaccine research programme

- AC Immune

Immunostimulants

71


disease vaccine - Atlas

Pharmaceuticals

Atlas Pharmaceuticals is developing an amyloid

beta vaccine formulated into a liposomal

adjuvant for the treatment and prevention of

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.

Immunostimulants

72


disease vaccine - DNAVEC/Eisai

DNAVEC and Eisai have entered into a drug

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

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.]

Immunostimulants

70


disease therapy - Thuris/D-Pharm

Thuris Corporation is investigating compounds

for the treatment of Alzheimer's disease. Thuris

is using its RapidAgingTM technology to identify

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

potential treatments.

Alzheimer's disease therapy research programme

- Thuris/D-Pharm

Undefined mechanism

69


disease therapy - Satori

Pharmaceuticals

Satori Pharmaceuticals is developing gamma-

secretase modulators as a disease modifying

therapy for Alzheimer's disease (AD). AD is

characterized by the formation of amyloid beta

(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.]


CT 0109 Cognition Therapeutics Owner USA Pharmaceutical Private

CT0093

CT0109

Amyloid oligomer small molecule Alzheimer's disease Preclinical Parenteral USA Kinexis Market Licensee World Company

Amyloid oligomer vaccine Neurodegenerative disorders Preclinical Parenteral USA University of California at Irvine Originator USA University N/A

Anti-amyloid oligomer MAb Parkinson's disease Preclinical Parenteral USA University of California at Irvine Owner USA University N/A

Anti-amyloid oligomer monoclonal antibody

AZ 12066871 Alzheimer's disease Preclinical Unknown route United Kingdom Astex Pharmaceuticals Originator USA Pharmaceutical Public

AZ-12066871 AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

AZ12066871

BACE1 inhibitors - Astex

Pharmaceuticals/AstraZenecaBeta-secretase inhibitors - Astex

Pharmaceuticals/AstraZenecaMemapsin-2 inhibitors - Astex

Pharmaceuticals/AstraZenecaBristol-Myers Squibb is developing gamma

secretase (gamma-secretase) inhibitors for the

treatment of Alzheimer's disease (AD). Lead

compounds from this programme include BMS

289948, BMS 299897 and BMS 433796.

BMS 289948 Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

The neurodegeneration observed in AD is thought

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 299897 Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

BMS 433796

BMS-289948

BMS-299897

BMS-433796

EVP 14936 Alzheimer's disease Preclinical PO USA Amorfix Life Sciences Collaborator Canada Biopharmaceutical Public

EVP 15962 EnVivo Pharmaceuticals Originator USA Biopharmaceutical Private

EVP-14936 EnVivo Pharmaceuticals Owner USA Biopharmaceutical Private

EVP-15962

Merck & Co. is developing small molecule

inhibitors of amyloid precursor protein secretase

(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-1 inhibitors - Merck & Co Alzheimer's disease Preclinical PO USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public

beta-secretase is a proteolytic enzyme involved

in the cleavage of amyloid precursor protein

(APP) to produce toxic beta-amyloid (Abeta)

peptides 40 and 42 [CONT.]

gamma-secretase inhibitors - Merck & Co Schering-Plough Originator USA Large Pharma, Pharmaceutical Public

BACE programme - Merck & Co

SCH 1375975

SCH 697466

SCH 723909

SCH 741216

SCH 745966

SCH 747123

SCH-1375975

SCH-745966

NGP 555 Alzheimer's disease Preclinical PO USA NeuroGenetic Pharmaceuticals Owner USA Pharmaceutical

NGP-555 TorreyPines Therapeutics Inc Originator USA Biopharmaceutical Public

NGP555

NGX 555

NGX555

anti-Abeta antibodies - Takeda Alzheimer's disease Preclinical Injection Japan Takeda Originator Japan Large Pharma, Pharmaceutical Public

BA 27 Takeda Owner Japan Large Pharma, Pharmaceutical Public

BA27

BC 05

BC05

Alzheimer's disease Preclinical Parenteral USA Centocor Originator USA Biopharmaceutical Public

Johnson & Johnson Pharmaceutical Research &

Development


AstraZeneca is developing compounds for the

treatment of anxiety and neurological disorders,

including affective disorders and Alzheimer's

disease. Preclinical development is ongoing in the

UK, US and Sweden.

5-HT1A receptor antagonists - AstraZeneca Opioid delta receptor agonists Alzheimer's disease Preclinical Unknown route Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

AstraZeneca and Columbis University Medical

Center are also collaborating to examine

neurogenesis as a potential pathway for

treament of depression and anxiety. [CONT.]

AZ 12320927 Serotonin 1A receptor antagonists Anxiety disorders Preclinical Unknown route United Kingdom AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

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

Eli Lilly is developing lentiviral vectors expressing

apolipoprotein E (apoE) isoforms for treatment of

Alzheimer's disease (AD). Development is at the

preclinical stage in the US.

Alzheimer's disease Preclinical Unknown route USA Eli Lilly Originator USA Large Pharma, Pharmaceutical Public

Studies have indicated that direct gene delivery

of apoE2 via intracerebral administration may

prevent or reduce brain amyloid-beta (Abeta)

burden and the subsequent development of

neuritic plaques. [CONT.]

Eli Lilly Owner USA Large Pharma, Pharmaceutical Public92

Research programme: apolipoprotein

E gene therapy - Eli Lilly

ApoE2 gene therapy - Eli Lilly Apolipoprotein E agonists

90

Research programme: anti-beta-

amyloid antibodies - Centocor/

Johnson & Johnson

Centocor and Johnson & Johnson Pharmaceutical

Research and Development are developing

monoclonal antibodies specific to a truncated

form of beta-amyloid (Abeta), for the treatment

of Alzheimer's disease. The truncated form of

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

Swedish mutation in APP [CONT.]

JRF/hAb11/1 Amyloid beta-protein inhibitors

91

Research programme: anxiety and

neurological disorder therapeutics -

AstraZeneca

89

Research programme: anti-beta

amyloid antibodies - Takeda

Takeda is developing passive immunotherapy for

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,

including meningoencephalitis, prompted Takeda

to develop antibodies against beta amyloid

(Abeta) as a potentially safer option.

Development is at the preclinical stage in Japan.

[CONT.]


88

Research programme: amyloid

precursor protein secretase

modulators - NeuroGenetic

Pharmaceuticals

NeuroGenetic Pharmaceuticals is developing

small molecule modulators of human amyloid

precursor protein secretase (gamma-secretase)

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

The company has identified a series of orally

available 2-aminothiazole derivatives that

lowered pathogenic beta-amyloid (Abeta)

Abeta42 levels and shifted the cleavage towards

shorter Abeta peptides (such as Abeta37 ,

Abeta38) [CONT.]


86



inhibitors - EnVivo

EnVivo Pharmaceuticals is developing small-

molecule, oral amyloid precursor protein

secretase (gamma-secretase) inhibitors for the

treatment of Alzheimer's disease (AD). The

company believes that its compounds are brain-

permeable and have disease-modifying potential.

Lead compounds identified under the programme

include EVP 14936 which has entered into

preclinical development in the US. [CONT.]

Amyloid precursor protein secretase inhibitors

87



inhibitors - Merck & Co


85



inhibitors - Bristol-Myers Squibb


84



inhibitors - Astex

Pharmaceuticals/AstraZeneca

Astex Pharmaceuticals and AstraZeneca are

collaborating on the development of a series of

pyrimidine compounds targeting the amyloid

precursor protein secretase, beta-secretase, a

key protein implicated in Alzheimer's disease.

Astex Pharmaceuticals, a structure-based drug

discovery company, is providing an initial series

of small-molecule, high affinity, beta-secretase

inhibitors. [CONT.]


83


oligomer therapeutics - Kinexis

Kinexis Inc., a life science R&D company, is

developing a variety of amyloid oligomer

therapeutics for the treatment of

neurodegenerative diseases. The company

exclusively licensed the intellectual property and

know-how for this programme from the

University of California, Irvine. [CONT.]

82


protein inhibitors - Cognition

Therapeutics

Cognition Therapeutics is developing small

molecule, amyloid beta-protein inhibitors, as a

disease-modifying treatment for Alzheimer's

disease. The lead candidates inhibit the activity

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 Preclinical Unknown route USA Merck & Co Market Licensee World Large Pharma, Pharmaceutical Public

The J. David Gladstone Institutes Originator USA Institution N/A

The J. David Gladstone Institutes Owner USA Institution N/A

COG 112 Alzheimer's disease Preclinical Unknown route USA Cognosci Owner USA Pharmaceutical Private

COG 133 Brain injuries Preclinical Unknown route USA Duke University Originator USA University N/A

COG 1410 Multiple sclerosis Preclinical Unknown route USA

COG 241 Subarachnoid haemorrhage Preclinical Unknown route USA

COG 68 Inflammatory bowel diseases Discontinued(Preclinical) Unknown route USA

COG112 Chronic lymphocytic leukaemia No development reported(Preclinical) Unknown route USA

COG133 Rheumatoid arthritis No development reported(Preclinical) Unknown route USA

COG1410 Parkinson's disease No development reported(Research) Unknown route USA

COG241

COG68

Alzheimer's disease Preclinical Unknown route USA Madera BioSciences Originator USA Biotechnology Private

Madera BioSciences Owner USA Biotechnology Private

BACE inhibitors - CoMentis Alzheimer's disease Preclinical PO USA Astellas Pharma Licensee World Large Pharma, Pharmaceutical Public

Disease modifying Alzheimer's disease therapy -

CoMentis

CoMentis Originator USA Biopharmaceutical Private

OM 991 CoMentis Owner USA Biopharmaceutical Private

OM 992 Oklahoma Medical Research Foundation Technology Provider USA Institution N/A

University of Illinois at Chicago Technology Provider USA University N/A

Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

Alzheimer's disease Preclinical Unknown route USA Johnson & Johnson Pharmaceutical Research &

Development


Johnson & Johnson Pharmaceutical Research &

Development

Owner USA Pharmaceutical Public

Merck & Co. in the US is developing brain-

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


SCH 1359113 Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

It is believed that the amyloid cascade plays a

significant role in the cause of Alzheimer's

disease. [CONT.]

SCH 1682496 Sunesis Pharmaceuticals Originator USA Biopharmaceutical Public

SCH 785532

SCH-1359113

SCH-1682496

SCH-785532

Alzheimer's disease Preclinical IV Switzerland Novartis Originator Switzerland Large Pharma, Pharmaceutical Public

Novartis Owner Switzerland Large Pharma, Pharmaceutical Public

WAC-547415 Alzheimer's disease Preclinical PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public

WAY-258131 Wyeth Originator USA Large Pharma, Pharmaceutical Public

WY-24454

BACE1 inhibitors - Vitae Alzheimer's disease Preclinical PO USA Boehringer Ingelheim Licensee World Large Pharma, Pharmaceutical Private

Beta secretase inhibitors - Vitae Vitae Pharmaceuticals Originator USA Pharmaceutical Private

Vitae Pharmaceuticals Owner USA Pharmaceutical Private

PD 0118057 Alzheimer's disease Preclinical Unknown route Japan, USA Astellas Pharma Originator Japan Large Pharma, Pharmaceutical Public

PD 0202091 Pfizer Originator USA Large Pharma, Pharmaceutical Public

Alzheimer's disease Preclinical Unknown route Switzerland Actelion Pharmaceuticals Originator Switzerland Large Pharma, Biopharmaceutical Public

104

Research programme: beta secretase

inhibitors - Actelion

Researchers at Actelion Pharmaceuticals are

investigating aspartyl protease inhibitors of beta

secretase (BACE, BACE1, beta amyloid precursor

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 inhibitor Amyloid beta-protein precursor inhibitors

102

Research programme: BACE1 protein

inhibitors - Vitae Pharmaceuticals

Vitae Pharmaceuticals, and Boehringer

Ingelheim, are developing oral BACE1 (bate site

APP cleaving enzyme 1) protein inhibitors for the


inhibitors have demonstrated the ability to cross

the blood-brain barrier and to lower brain

amyloid beta (Abeta) peptide following a single

oral dose in preclinical, in vivo models of AD.

[CONT.]


103

Research programme: beta amyloid

aggregation inhibitors - Astellas

Pharma/Pfizer

Pfizer and Astellas Pharma are developing

amyloid beta peptide (Abeta) aggregation


disease. Formation of insoluble plaques caused

by aggregation of Abeta is thought to initiate a

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.]


101


inhibitors - Pfizer

Pfizer is developing orally active, small molecule

inhibitors of beta-secretase (BACE1) for the

treatment of Alzheimer's disease. beta-secretase

is a human brain protease that catalyzes the first

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

is underway in the US. [CONT.]


100


inhibitors - Novartis

Novartis is developing cyclic sulfoxide

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

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.]


98


inhibitors - Johnson & Johnson

Johnson & Johnson Pharmaceutical R&D is

developing a series of BACE1 (beta-amyloid site

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-

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

oligomers and fibrils [CONT.]


99


inhibitors - Merck and Co


96


inhibitors - Astellas

Pharma/CoMentis

CoMentis (formerly Zapaq) and Astellas Pharma

are co-developing orally available, small

molecule inhibitors of BACE1 (beta-amyloid

converting enzyme 1 or memapsin 2) as disease-

modifying agents for Alzheimer's disease (AD).

beta-secretase is a human brain aspartic

protease that catalyses the rate-limiting step in

amyloid-beta (Abeta) peptide production, a key

event in the progression of AD. [CONT.]


97


inhibitors - Bristol-Myers Squibb

Bristol-Myers Squibb is developing BACE1 (beta-

secretase) inhibitors for the treatment of

Alzheimer's disease. BACE is a human brain

protease that catalyzes the first 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.

[CONT.]

BMS 782450 BACE1 protein inhibitors

95


E-targeted Alzheimer's disease

therapeutics - Madera Biosciences

Madera Biosciences is developing small molecule

compounds that increase the expression of

apolipoprotein E (apoE) for the treatment of

Alzheimer's disease (AD) in the US. Through the

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.]

Apolipoprotein E modulators

93


E therapies - Gladstone

Institutes/Merck

Merck & Co., Inc. is collaborating with the J.

David Gladstone Institutes in the development of

a treatment for neurodegenerative diseases

linked to apolipoprotein E (apoE)-regulated

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

function. [CONT.]

Undefined mechanism

94


E-mimetic peptide therapeutics -

Cognosci Inc.

Cognosci Inc. of Research Triangle Park (North

Carolina, US) is developing small molecule

apolipoprotein E (apoE)-mimetic peptides of ten

to seventeen amino acids for the treatment of

multiple sclerosis (MS), traumatic brain injury,

subarachnoid haemorrhage and Alzheimer's

disease. These compounds may also have

potential in the treatment of rheumatoid arthritis

and Parkinson's disease. [CONT.]

Apolipoprotein E agonists

Actelion Pharmaceuticals Owner Switzerland Large Pharma, Biopharmaceutical Public

Abeta inhibitors - Prana Biotechnology Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO Australia Prana Biotechnology Originator Australia Biotechnology Public

Metallocomplex programme - Prana

Biotechnology

Chelating agents Alzheimer's disease (Diagnosis) Research PO Australia Prana Biotechnology Owner Australia Biotechnology Public

VK-11 Diagnostic imaging enhancers

VK-12

Abeta ligands - Affibody Alzheimer's disease Preclinical Unknown route Sweden Affibody Originator Sweden Biotechnology Private

Affibody® molecules Affibody Owner Sweden Biotechnology Private

Beta-amyloid ligands - Affibody

beta-amyloid secretion inhibitors Alzheimer's disease Preclinical Unknown route Italy Chiesi Originator Italy Pharmaceutical Private

CHF 4801 Chiesi Owner Italy Pharmaceutical Private

CHF 5022

CHF-5077

CHF4801

CHF5022

CHF5077

CHF5096

CHF5105

Alzheimer's disease Preclinical PO Japan, USA Janssen Pharmaceuticals Licensee USA Pharmaceutical Public

Shionogi Originator Japan Large Pharma, Pharmaceutical Public

Shionogi Owner Japan Large Pharma, Pharmaceutical Public

A 705253 Alzheimer's disease Preclinical Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

A-705253 AbbVie Owner USA Biopharmaceutical Public

APH 0802 Alzheimer's disease Preclinical PO USA Aphios Corporation Originator USA Biopharmaceutical Private

APH-0802 Cachexia Preclinical PO USA Aphios Corporation Owner USA Biopharmaceutical Private

Cannabinoid therapeutics research programme -

Aphios Corporation

Cancer pain Preclinical PO USA

Delta-9-tetrahydrocannabinol Drug abuse Preclinical PO USA

Delta-9-tetrahydrocannabinolic acid Nausea and vomiting Preclinical PO USA

Delta-9-THC

Delta-9-THC nanotech formulation

Delta-9-THCA

Cell mobility activators - Pharmaxon Cell movement activators Spinal cord injuries Preclinical Unknown route France CNRS Originator France Institution N/A

Polysialyl neural cell adhesion molecule

mimotope

Polysialyl neural cell-adhesion-molecule-agonists Alzheimer's disease Research Unknown route France Pharmaxon Licensee World Biopharmaceutical Private

PR-21C Mild cognitive impairment Research Unknown route France Schafer-N Originator Denmark Biotechnology Private

PR-21S Universite de la Mediterranee Originator France University N/A

PSA-NCAM mimotope University Medical Center Hamburg-Eppendorf Originator Germany University N/A

AGT 110 Acetylcholinesterase inhibitors Alzheimer's disease (Diagnosis) Preclinical IV USA ArmaGen Technologies Originator USA Biotechnology Private

AGT 115 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical IV USA ArmaGen Technologies Owner USA Biotechnology Private

AGT 120 Erythropoietin receptor modulators Parkinson's disease Preclinical IV USA

AGT 160 Glial cell line-derived neurotrophic factor

modulators

Poisoning Preclinical Unknown route USA

AGT 185 Tumour necrosis factor alpha inhibitors Stroke Preclinical IV USA

AGT 190 Tumour necrosis factor decoy receptor

modulators

Brain cancer No development reported(Preclinical) IV USA

AGT 3 Tumour necrosis factor inhibitors Brain disorders No development reported(Preclinical) IV USA

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

PA 1637 Alzheimer's disease Preclinical Unknown route France PALUMED Originator France Biotechnology Private

PA1637 PALUMED Owner France Biotechnology Private

ST 1859 Alzheimer's disease Preclinical Unknown route Italy sigma-tau SpA Originator Italy Pharmaceutical Private

ST 1936 Depressive disorders Preclinical Unknown route Italy sigma-tau SpA Owner Italy Pharmaceutical Private

ST 2472 Schizophrenia Preclinical Unknown route Italy

ST1936

ST2472

ANAVEX 1 41 Calcium channel antagonists Alzheimer's disease Preclinical IV Europe Anavex Life Sciences Originator Switzerland Biopharmaceutical Public

ANAVEX 1-41 Chloride channel modulators Alzheimer's disease Preclinical PO Europe Anavex Life Sciences Owner Switzerland Biopharmaceutical Public

ANAVEX 19-144 Muscarinic M1 receptor agonists Epilepsy Preclinical Unknown route Europe

Muscarinic M2 receptor antagonists Major depressive disorder Preclinical Unknown route Europe

Muscarinic M3 receptor antagonists Stroke Preclinical Unknown route Germany

NMDA receptor antagonists

Serotonin modulators

Sigma-1 receptor agonists

Sodium channel antagonists

Sodium channel modulators

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO USA Intra-Cellular Therapies Originator USA Company

Dopamine D1 receptor agonists Intra-Cellular Therapies Owner USA Company

Dopamine receptor agonists Takeda Licensee World Large Pharma, Pharmaceutical Public

116

Research programme: CNS disorders

therapeutics - Intra-Cellular

Therapies

Intra-Cellular Therapies is developing orally-

available, small molecule therapeutics for the


(CNS) disorders, including Alzheimer's disease

(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-

licensed candidates. [CONT.]

ITI-009

115


therapeutics - Anavex Life Sciences

Anavex Life Sciences is developing compounds

targeted at sigma receptors for the treatment of

the central nervous system (CNS) disorders

Alzheimer's disease, epilepsy, depression and

stroke. Pharmacological research has indicated

that sigma-1 and sigma-2 receptors act as

intracellular amplifiers, creating a supersensitive

state of signal transduction in biochemical

pathways, which might contribute to these

disorders [CONT.]

114

Research programme: CNS disorder

therapies - sigma-tau

sigma-tau has a research programme directed at

disorders of the central nervous system (CNS)

and peripheral nervous system (PNS). Lead

compounds from this programme include ST

2472 and ST 1859 for the treatment of

schizophrenia and Alzheimer's disease,

respectively. Another lead candidate, ST 1936, is

also in development as a treatment for unipolar

depressive disorders. [CONT.]

Undefined mechanism

113

Research programme: chelating

agents - PALUMED

PALUMED SA, in France, is researching copper

chelating agents for the treatment of Alzheimer's

disease (AD) including lead candidate PA 1637.

Preclinical development of PA 1637 is ongoing

and PALUMED is preparing it to enter clinical

trials. [CONT.]

Chelating agents

112

Research programme: central

nervous system therapeutics -

ArmaGen

ArmaGen is developing therapies for the

treatment of central nervous system (CNS)

disorders utilising their trojan horse delivery

system. This delivery system involves binding a

substrate capable of crossing the blood brain

barrier (BBB) to a therapeutic agent. [CONT.]

111

Research programme: cell movement

activators - Pharmaxon

Pharmaxon is developing compounds that

specifically stimulate neural cell mobility and

neuroplasticity for the treatment of spinal cord

injuries as well as mild cognitive impairment and

Alzheimer's disease. A lead candidate generated

from this research is a polysialyl neural cell

adhesion molecule (PSA-NCAM) mimotope (a

cyclic 12-amino acid peptide that can

conformationally mimic antigenic specificity)

[CONT.]

109

Research programme: calpain

inhibitors - AbbVie

AbbVie (formerly Abbott Laboratories) is

developing calpain inhibitors 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. [CONT.]

Calpain inhibitors

110

Research programme: cannabinoid

therapeutics - Aphios Corporation

The US biopharmaceutical company Aphios

Corporation is developing natural cannabinoid

products, including lead candidate APH 0802,

derived from the marijuana plant Cannabis

sativa, for the treatment of a marijuana

addiction, cancer pain, cachexia in AIDS patients,

nausea and vomiting, and relief to Alzheimer's

patients while increasing their appetite. [CONT.]

Cannabinoid receptor agonists

108

Research programme: beta-secretase

inhibitors - Janssen/Shionogi

Janssen Pharmaceuticals and Shionogi are

collaborating to discover, develop and

commercialise small molecule oral beta-

secretase (BACE) (amyloid precursor protein

secretase) inhibitors for the treatment of

Alzheimer's disease. Development is at the

preclinical stage in Japan and the US. [CONT.]


107

Research programme: beta-amyloid

secretion inhibitors - Chiesi

Chiesi in Italy is developing flurbiprofen

analogues for the potential treatment of patients

with Alzheimer's disease. The chronic use of a

subset of non-steroidal anti-inflammatory drugs

(flurbiprofen, ibuprofen and indomethacin) has

been reported to selectively inhibit the production

of beta amyloid1-42 (Abeta42) in vitro and limit

the progression of Abeta plaque pathology in

mice over expressing human amyloid precursor

protein [CONT.]


106


ligands - Affibody

Affibody AB is developing Affibody® molecules as

small protein ligands that target beta-amyloid

(Abeta) for the treatment of Alzheimer's disease

(AD). Such ligands stabilise the Abeta peptide

and inhibits the formation of toxic Abeta fibrils

and plaques in the brain. Development of lead

candidates is at the preclinical stage in Sweden.

[CONT.]


104

Research programme: beta secretase

inhibitors - Actelion

Researchers at Actelion Pharmaceuticals are

investigating aspartyl protease inhibitors of beta

secretase (BACE, BACE1, beta amyloid precursor

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 inhibitor Amyloid beta-protein precursor inhibitors

105


inhibitors - Prana Biotechnology

Prana Biotechnology is developing a compound

library comprising a next-generation class of

orally available, platinum-based complexes

('metallocomplexes') with 1,10-phenanthroline-

derived ligands as beta-amyloid (Abeta)

inhibitors for the treatment of neurodegenerative

disorders, particularly Alzheimer's disease (AD).

Such compounds bind and block the actual metal-

binding site on Abeta peptide in the brain

[CONT.]

Type 1 cyclic nucleotide phosphodiesterase

inhibitors3-Methoxy-pregnenolone Microtubule-associated protein stimulants Alzheimer's disease Preclinical Parenteral France Mapreg Originator France Biotechnology Private

Pregnenolone analogues Tubulin polymerisation promoters Brain injuries Preclinical Parenteral France Mapreg Owner France Biotechnology Private

Pregnenolone derivatives Depressive disorders Preclinical Parenteral France

Schizophrenia Preclinical Parenteral France

Spinal cord injuries Preclinical Parenteral France

Stroke Preclinical Parenteral France

Alzheimer's disease Preclinical Unknown route Canada MedGenesis Therapeutix Originator Canada Biopharmaceutical Private

Glioblastoma Preclinical Unknown route Canada MedGenesis Therapeutix Owner Canada Biopharmaceutical Private

Parkinson's disease Preclinical Unknown route Canada

CB 2433 Alzheimer's disease Preclinical Unknown route USA Cenomed BioSciences Licensee World Biopharmaceutical Private

CB-2 Mild cognitive impairment Preclinical Unknown route USA Medical College of Georgia Originator USA Institution N/A

433 Medical College of Georgia Owner USA Institution N/A

CB-2433

CB2433

CM 2433

CM 2450

CM-2

433

CM-2

450

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO United Kingdom Nonindustrial source Originator Unknown Institution N/A

Antioxidants Cancer Research Unknown route United Kingdom Nonindustrial source Owner Unknown Institution N/A

Apoptosis inhibitors ReGen Therapeutics Market Licensee United Kingdom Company

Cell differentiation stimulants

Minozac Alzheimer's disease Preclinical PO Canada, USA Chinese Academy of Sciences Collaborator China Institution N/A

MW 015188WH Rheumatoid arthritis Preclinical PO Canada, USA InnovatePharma Collaborator USA Pharmaceutical Private

MW01-5-188WH Alzheimer's disease Discontinued(Preclinical) PO China Northwestern University Originator USA University N/A

TT302 Brain injuries Discontinued(Preclinical) PO Canada, China Northwestern University Owner USA University N/A

Multiple sclerosis Discontinued(Preclinical) PO Canada, China, USA Transition Therapeutics Licensee World Biopharmaceutical Public

Parkinson's disease Discontinued(Preclinical) PO Canada, USA University of California at Los Angeles Collaborator USA University N/A

Cholinesterase inhibitors Alzheimer's disease Preclinical Unknown route USA ChemDiv Originator USA CRO Private

G protein-coupled receptor modulators Cognition disorders Preclinical Unknown route USA ChemDiv Owner USA CRO Private

NMDA receptor antagonists

Serotonin 6 receptor antagonists

Alzheimer's disease Preclinical Unknown route Italy Siena Biotech Originator Italy Company

Siena Biotech Owner Italy Company

Alzheimer's disease Preclinical Unknown route USA Diaxonhit Originator France Pharmaceutical

Down syndrome Preclinical Unknown route USA Diaxonhit Owner France Pharmaceutical

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

CA 074Me Cathepsin B inhibitors American Life Science Pharmaceuticals Owner USA Pharmaceutical

CA074Me Endopeptidase inhibitors

E 64d

E64d

Alzheimer's disease Preclinical Unknown route USA Chicago Labs Originator USA Company

Pain Preclinical Unknown route USA Chicago Labs Owner USA Company

Stroke Preclinical Unknown route USA

ESN-282 G protein-coupled receptor modulators Alzheimer's disease Preclinical Unknown route Belgium Euroscreen Originator Belgium Company

ESN-401 G-protein coupled receptor 43 modulators Amyotrophic lateral sclerosis Preclinical Unknown route Belgium Euroscreen Owner Belgium Company

ESN-502 Brain injuries Preclinical Unknown route Belgium

ESN-603 Parkinson's disease Preclinical Unknown route Belgium

Ulcerative colitis Preclinical Unknown route Belgium

Obesity Research Unknown route Belgium

Type 2 diabetes mellitus Research Unknown route Belgium

Inflammation No development reported(Research) Unknown route Belgium

SPH 1285 Alzheimer's disease Preclinical Unknown route Austria Sanochemia Pharmazeutika Originator Austria Pharmaceutical Public

SPH 1286 Dementia Preclinical Unknown route Austria, United Kingdom Sanochemia Pharmazeutika Owner Austria Pharmaceutical Public

SPH 1371 Neurological disorders Preclinical Unknown route Austria, United Kingdom

128

Research programme: galantamine

derivatives - Sanochemia

Pharmazeutika

Sanochemia Pharmazeutika is investigating

galantamine derivatives as potential treatments

for various neurodegenerative disorders,

including dementia, stroke, brain injury,

Parkinson's disease, Alzheimer's disease and

neuropathic pain. The company's most developed

molecule [SPH 1285] has a partially novel

mechansim of action and is a candidate for

phase I clinical trials. [CONT.]

Acetylcholinesterase inhibitors

127

Research programme: G protein-

coupled receptor modulators -

Euroscreen

Euroscreen in Belgium has a broad research

programme focussed on discovering small

molecule therapeutics that target G protein-

coupled receptors (GPCRs). Lead compounds

under investigation include ESN 282, a GPR43

modulator in development for ulcerative collitis,

and ESN 502, a GPR modulator investigated for

neurodegenerative diseases such as Alzheimer's,

Parkinson's, amyotropic lateral sclerosis (ALS)

and traumatic brain injury [CONT.]

126

Research programme: endothelin

receptor antagonists - Chicago Labs

Chicago Labs is developing endothelin (ET)

receptor antagonists for the treatment of pain,

stroke, and Alzheimer's disease. Endothelin

receptors are prevalent throughout the

vasculature and are responsible for vasodilation

and vasoconstriction. Development is at the


Endothelin receptor antagonists

124

Research programme: DYRK

inhibitors - Diaxonhit

Diaxonhit is developing small molecule, selective

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

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.]

DYRK kinase inhibitors

125

Research programme: endopeptidase

inhibitors - American Life Science

Pharmaceuticals

American Life Science Pharmaceuticals is

developing small molecule inhibitors of

proprietary endopeptidase targets for the

treatment of Alzheimer's disease. The company

is focusing on the development of secretase and

cathepsin B endopeptidase targets. Secretases

cleave amyloid precursor protein (APP) into beta-

amyloid (Abeta) peptides which are thought to be

responsible for the pathology of Alzheimer's

disease [CONT.]

123

Research programme: DKK1

antagonists - Siena Biotech

Siena Biotech is developing small molecule

selective antagonists of the Dickkopf-1 (DKK1)

protein as a treatment for Alzheimers disease

(AD). It has been demonstrated that DKK1

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

suffering from AD. [CONT.]

Wnt protein modulators

121

Research programme: cytokine

inhibitors - Transition Therapeutics

Transition Therapeutics is developing small

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

the potential treatment of Alzheimer's disease

and rheumatoid arthritis. Development for the

latter indication is being conducted in conjunction

with the University of California at Los Angeles

(California, USA) [CONT.]

Cytokine inhibitors

122

Research programme: dimebolin

analogues - ChemDiv

ChemDiv is undertaking a research programme

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

been found to penetrate the blood-brain barrier

and possess promising cognition-enhancing

properties. Optimised lead compounds are

undergoing preclinical testing in the US. [CONT.]

120

Research programme: colostrinin

constituent peptides - ReGen

Therapeutics

ReGen Therapeutics Plc is characterising of the

biologically active peptide constituents of

Colostinin™ in order to identify properties that

might lend them towards development as

pharmaceutical agents for CNS

neurodegenerative diseases and cancer. The

company hopes to identify smaller molecular

weight therapeutics that have similar or greater

activity than Colostrinin™. [CONT.]

Colostinin™

119

Research programme: cognitive

disorders therapeutics - Cenomed

BioSciences

Cenomed BioSciences, in collaboration with the

Medical College of Georgia Research Institute, is

developing small molecules that target

components of acetylcholine neurons and thereby

enhance cholinergic function. These agents are

being developed to treat cognitive disorders such

as mild cognitive impairment and Alzheimer's

disease, while avoiding cholerinergic side effects.

[CONT.]

Cholinergic receptor modulators

118


therapeutics - MedGenesis

Therapeutix

MedGenesis Therapeutix Inc is developing

compounds to treat diseases of the central

nervous system (CNS) including Alzheimer's

disease, Parkinson's disease and brain cancers.

The company is using its Convection Enhanced

Delivery (CED) methods to target and transport

therapeutic agents to the relevant area in the

CNS. [CONT.]

Undefined mechanism

116


therapeutics - Intra-Cellular

Therapies

Intra-Cellular Therapies is developing orally-

available, small molecule therapeutics for the


(CNS) disorders, including Alzheimer's disease

(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-

licensed candidates. [CONT.]

ITI-009

117


therapeutics - Mapreg

Mapreg SAS of France is developing a series of

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

and Alzheimers's disease. These pregnenolone

derivatives do not exhibit metabolic interactions

with other steroid hormones and are designed for

administration by injection with the ability to

cross the blood-brain barrier. Development is at

the preclinical stage in France. [CONT.]

SPH 1373 Neuropathic pain Preclinical Unknown route Austria

SPH 1375

SPH-1285

SPH-1286

SPH-1371

SPH-1373

SPH-1375

SPH1285

Galantamine pro-drug - Galantos Pharma Acetylcholinesterase inhibitors Alzheimer's disease Preclinical Intranasal Germany Galantos Pharma Originator Germany Pharmaceutical Private

GLN 1062 Nicotinic receptor modulators Alzheimer's disease Preclinical IV Germany Galantos Pharma Owner Germany Pharmaceutical Private

GLN-1062

GLN1062

Memogain®

Pro-galantamine - Galantos Pharma

MRK 003 Amyloid precursor protein secretase inhibitors Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

MRK 560 Notch signalling pathway inhibitors Cancer Preclinical PO USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public

MRK-003

MRK-560

2B3 201 Immunosuppressants Inflammation Preclinical Unknown route Netherlands to-BBB technologies Originator Netherlands Biotechnology Private

2B3-201 Steroid receptor agonists Multiple sclerosis Preclinical Unknown route Netherlands VIB Originator Belgium Institution N/A

Brain-targeted liposomal methylprednisolone Undefined mechanism Alzheimer's disease Research Unknown route Netherlands

Glutathione pegylated liposomal

methylprednisolone

Brain cancer Research Unknown route Netherlands

CNS disorders Research Unknown route Netherlands

Alzheimer's disease Preclinical Unknown route USA ALS Biopharma Originator USA Biotechnology Private

Amyotrophic lateral sclerosis Preclinical Unknown route USA ALS Biopharma Owner USA Biotechnology Private

Vybion Technology Provider USA Company

Alzheimer's disease Preclinical Unknown route USA Ligand Pharmaceuticals Originator USA Biotechnology Public

Attention-deficit hyperactivity disorder Preclinical Unknown route USA Ligand Pharmaceuticals Owner USA Biotechnology Public

Narcolepsy Preclinical Unknown route USA

Schizophrenia Preclinical Unknown route USA

EVX 001688 Alzheimer's disease Preclinical PO Canada, USA CHDI Collaborator USA Biotechnology Private

EVX001688 Huntington's disease Preclinical PO Canada, USA EnVivo Pharmaceuticals Licensee World Biopharmaceutical Private

HDAC inhibitors - EnVivo Neurodegenerative disorders Preclinical PO Canada, USA MethylGene Originator Canada Biopharmaceutical Public

HDACi - EnVivo Parkinson's disease Preclinical PO Canada, USA Mirati Therapeutics Owner USA Biopharmaceutical Public

Isotope-selective HDAC inhibitors (Series B) -

EnVivoCNS 101 Alzheimer's disease Preclinical Unknown route USA Coyote Pharmaceuticals Originator USA Biopharmaceutical Private

CNS 102 Amyotrophic lateral sclerosis Preclinical Unknown route USA Coyote Pharmaceuticals Owner USA Biopharmaceutical Private

CNS 101

CNS 102

CNS-101

CNS-102

CNS101

CNS102

NPT-007 Alpha-synuclein modulators Alzheimer's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Originator USA Biotechnology

NPT-014 Amyloid beta-protein modulators Parkinson's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Owner USA Biotechnology

NPT-088 Tau protein modulators

NPT007

NPT014

NPT088

MNLP462a Glucose modulators Alzheimer's disease Preclinical PO United Kingdom MNLpharma Originator United Kingdom Pharmaceutical Private

SMT 14400 Haemoglobin modulators Cancer No development reported(Preclinical) PO United Kingdom Summit plc Owner World Biotechnology Public

SMT C2100 Hepatitis C virus NS3 protein modulators Diabetes mellitus No development reported(Preclinical) PO United Kingdom

SMT-14224 Hexosaminidase C inhibitors Viral infections No development reported(Preclinical) PO Europe

SMT-14400 Immunomodulators Hepatitis C No development reported(Research) PO United Kingdom

SMT-C2100 Immunostimulants

SMT14224 Triglyceride modulators

SMT14400

VOX 14400

VOX-14400

VOX14400

AD 0802 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral Sweden BioArctic Neuroscience Originator Sweden Biotechnology Private

AD-0802 Amyloid beta-protein inhibitors Parkinson's disease Preclinical Parenteral Sweden BioArctic Neuroscience Owner Sweden Biotechnology Private

AD0802 Immunomodulators

Alzheimer's vaccine - BioArctic Neuroscience

BAN 2203

BAN-2203

BAN2203

Monoclonal antibodies - BioArctic Neuroscience

PD 0805

PD-0805

PD0805

Omni-Raf inhibitors - Plexxikon Fms-like tyrosine kinase 3 inhibitors Alzheimer's disease Preclinical PO USA Plexxikon Originator USA Pharmaceutical Private

PLX FK1 Proto-oncogene protein b-raf modulators Cancer Preclinical PO USA Plexxikon Owner USA Pharmaceutical Private

PLX 7486 Raf kinase inhibitors Inflammation Preclinical PO USA139

Research programme: kinase

inhibitors - Plexxikon

Plexxikon (a Daiichi Sankyo subsidiary) is

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)

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.]

138

Research programme:

Immunotherapeutics - BioArctic

Neuroscience

BioArctic Neuroscience in Sweden is developing

immunotherapeutics, including monoclonal

antibodies and vaccines, for the treatment of

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

(PD). The company's proprietary technology

platform is used to isolate proteins implicated in

neurological disorders, such as beta-amyloid and

alpha-synuclein, study their aggregation

properties, prepare and stabilise other

protofibrils, and develop protofibril specific

monoclonal antibodies [CONT.]

137

Research programme: imino sugar

therapeutics - Summit

Summit Corporation plc (VASTox) is developing

orally available, small molecule imino sugar


disease. The compounds were also being

developed for the treatment of hepatitis C,

diabetes mellitus and cancer, but no recent

development has been reported in these

indications. [CONT.]

136

Research programme: Ig fusion

GAIM dimers - NeuroPhage

Pharmaceuticals

Neurophage Pharmaceuticals is developing

therapies targeted at protein misfolding. The

proprietary phage technology used results in

products with a novel mechanism of action based

on a general amyloid interaction motif (GAIM).

The motif is characteristic of distinctive, recurring

components of protein structures and interaction,

including those of pathological protein

aggregates that are hallmarks of both

Alzheimer's and Parkinson's diseases [CONT.]

135

Research programme: homeostasis

modulators - Coyote Pharmaceuticals

Coyote Pharmaceuticals is developing therapies

that modulate homeostasis for the treatment of

diseases with large unmet medical needs in

several therapeutic areas, including

neurodegenerative, cardiovascular, oncology,

and inflammatory areas. The way that these

therapies modulate homeostasis may include

interactions with molecular chaperones, heat

shock proteins, ubiquitin proteasomes, and DNA-

RNA transcriptional regulators of homeostasis

network components [CONT.]

Heat-shock protein stimulants

134

Research programme: histone

deacetylase inhibitors - EnVivo

Pharmaceuticals

EnVivo Pharmaceuticals is undertaking a

research programme to develop a series of small

molecule, orally available, histone deacetylase

(HDAC) inhibitors for the treatment of

neurodegenerative disorders, including

Parkinson's disease (PD), Huntington's disease

(HD), dementia and Alzheimer's disease (AD).

These isotype-selective, brain-permeable HDAC

inhibitors have been exclusively in-licensed from

MethylGene which were generated using the

company's HDAC technology [CONT.]

Histone deacetylase inhibitors

133

Research programme: histamine H3

receptor antagonists - Ligand

Ligand Pharmaceuticals is developing histamine

H3 antagonists for the treatment of sleep

disorders (narcolepsy), attention deficit

hyperactivity disorder (ADHD) and cognitive

disorders (schizophrenia and Alzheimer's

disease). The H3 receptor modulates histamine

release in the brain, controlling the release of

excitatory neurotransmitters such as glutamate

and acetylcholine by stimulating H1 receptors

[CONT.]

Histamine H3 receptor antagonists

132

Research programme: heat shock

protein 70 inhibitors - ALS

Biopharma

ALS Biopharma is developing brain-penetrant

inducers of heat shock protein 70 (Hsp70), for

the treatment of neurodegenerative disorders

such as Alzheimer's disease and amytrophic

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.

HSP70 heat shock protein inhibitors

131

Research programme: glutathione-

pegylated liposome therapeutics - to-

BBB

to-BBB is developing therapeutics formulated

using its proprietary glutathione-pegylated

liposomes for the treatment of Alzheimer's

disease, brain cancer and CNS disorders.

Traditionally, targeting these indications has

been difficult due to the existence of the blood-

brain barrier which impedes the access of many

therapeutic agents to the brain. [CONT.]

130

Research programme: gamma

secretase inhibitors - Merck

Merck & Co. is developing small molecule

inhibitors of human amyloid precursor protein

secretase (gamma-secretase) for the treatment

of Alzheimer's disease (AD) and cancer. Various

classes of potent, functionally active gamma-

secretase inhibitors have been discovered and

characterised including benzodiazepine

derivatives, aryl sulfones and [4.2.1]-bicyclo-

based sulfonamides. [CONT.]

129


prodrug - Galantos Pharma

Galantos Pharma GmbH is developing an inactive

prodrug of galantamine, GLN 1062, for the


prodrug is proposed to be an improved version of

the acetylcholinesterase inhibitor and nicotinic

receptor modulator galantamine, which is

conventionally used for the treatment of mild-to-

moderate AD [see separate profile for

galantamine]. [CONT.]

128


derivatives - Sanochemia

Pharmazeutika

Sanochemia Pharmazeutika is investigating

galantamine derivatives as potential treatments

for various neurodegenerative disorders,

including dementia, stroke, brain injury,

Parkinson's disease, Alzheimer's disease and

neuropathic pain. The company's most developed

molecule [SPH 1285] has a partially novel

mechansim of action and is a candidate for

phase I clinical trials. [CONT.]

Acetylcholinesterase inhibitors

PLX-FK1 TrkA receptor antagonists Multiple sclerosis Preclinical PO USA

PLX4720 TrkB receptor antagonists Polycystic kidney disease Preclinical PO USA

PLX7486 TrkC receptor antagonists Solid tumours Preclinical PO USA

PLX7486-TsOH Vascular endothelial growth factor receptor-1

antagonistsAMP activated protein kinase modulators Alzheimer's disease Preclinical Parenteral USA National Institutes of Health (USA) Funder USA Institution N/A

Amyloid beta-protein inhibitors Neurotez Originator USA Biotechnology Private

Neurotez Owner USA Biotechnology Private

VTP 4 Alzheimer's disease Preclinical PO USA Vitae Pharmaceuticals Originator USA Pharmaceutical Private

VTP-4 Atherosclerosis Preclinical PO USA Vitae Pharmaceuticals Owner USA Pharmaceutical Private

Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Merck & Co Owner USA Large Pharma, Pharmaceutical Public

BT 2111 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Parenteral Canada biOasis Technologies Originator USA Biotechnology Private

BT 2211 Biological transport stimulants Brain metastases Preclinical Parenteral Canada biOasis Technologies Owner Canada Biotechnology Private

BT-2111 Enzyme replacements Lysosomal storage diseases Preclinical IV Canada Texas Tech University Health Sciences Center Collaborator USA University N/A

BT-2211 Transferrin receptor modulators University of British Columbia Originator Canada University N/A

BT2111

BT2211

Herceptin®-BT2111

D-Pharm in Israel is developing small molecule,

lipophilic, membrane activated, transition-metal

ion chelators for the treatment of Alzheimer's

disease.

DP 460 Alzheimer's disease Preclinical PO Israel D-Pharm Originator Israel Pharmaceutical Private

The company has selected a lead compound,

called DP 460. DP 460, a derivative of the

calcium chelator BAPTA, showed selective

membrane-dependent modulation of copper and

zinc homeostasis. [CONT.]

DP-460 Amyotrophic lateral sclerosis Discontinued(Preclinical) PO Israel D-Pharm Owner Israel Pharmaceutical Private

ADX 47273 Alzheimer's disease Preclinical PO Switzerland Addex Pharmaceuticals Originator Switzerland Pharmaceutical Public

ADX 50938 Cognition disorders Preclinical PO Switzerland Addex Therapeutics Owner Switzerland Pharmaceutical Public

ADX 63365 Schizophrenia Preclinical PO Switzerland

ADX47273

ADX50938

ADX63365 (mGluR5 PAMb)

ADX63365 (mGluR5 positive allosteric modulator

[PAM])CDPPB

Metabotropic glutamate receptor-5 modulators -

AddexmGluR5 modulators - Addex

MPAC - Prana Biotechnologies Alpha-synuclein inhibitors Age-related macular degeneration Preclinical Unknown route Australia Prana Biotechnology Originator Australia Biotechnology Public

PBT 434 Chelating agents Alzheimer's disease Preclinical Unknown route Australia Prana Biotechnology Owner Australia Biotechnology Public

PBT-434 Iron chelating agents Parkinson's disease Preclinical PO Australia The Michael J. Fox Foundation for Parkinsons Research Funder USA Institution N/A

PBT3 series - Prana Biotechnologies

PBT4 series - Prana Biotechnologies

PBT434

1A10 Amyloid beta-protein inhibitors Age-related macular degeneration Preclinical Parenteral USA Immuno-Biological Laboratories Originator Japan Company

8,20E+02 Amyloid inhibitors Alzheimer's disease Preclinical IV USA Intellect Neurosciences Licensee USA Biopharmaceutical Public

Anti-Abeta monoclonal antibodies Antioxidants Alzheimer's disease Preclinical Parenteral USA MRC Technology Technology Provider United Kingdom Company

IN N01 Protein aggregation inhibitors Glaucoma Preclinical Parenteral USA Northwestern University Originator USA University N/A

IN-N01 Tau protein inhibitors

IN-N01-OX2

N01-OX2

T01-OX2

tauC3

TOC 1

TOC-1

CDD 0097 Muscarinic M1 receptor agonists Alzheimer's disease Preclinical Unknown route USA Mithridion Licensee USA Biopharmaceutical

CDD 0098J Muscarinic receptor agonists Schizophrenia Preclinical Unknown route USA University of Toledo Originator USA University N/A

CDD 0199J University of Toledo Owner USA University N/A

CDD 0304

CDD 0312

CDD 0313

CDD 0314

CDD 0316

CDD 0317

CDD 0322

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

Alzheimer's disease Preclinical Parenteral Belgium, Germany Ablynx Originator Belgium Biopharmaceutical Private

Autoimmune disorders Preclinical Parenteral Belgium, Germany Boehringer Ingelheim Originator Germany Large Pharma, Pharmaceutical Private

Cancer Preclinical Parenteral Belgium, Germany

Respiratory tract disorders Preclinical Parenteral Belgium, Germany

NNI 362 Alzheimer's disease Preclinical PO USA Neuronascent Originator USA Biotechnology Private

NNI 370 Parkinson's disease Research PO USA Neuronascent Owner USA Biotechnology Private

NNI-362

150

Research programme:

neurodegenerative disease

therapeutics - Neuronascent

Neuronascent is developing a series of chemically

diverse neurogenic compounds as disease-

modifying drugs for the treatment of

neurodegenerative diseases including Alzheimer's

disease (AD) and Parkinson's disease. The

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.]

149

Research programme: Nanobodies -

Ablynx/Boehringer Ingelheim

Boehringer Ingelheim and Ablynx are

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

respiratory disorders. Nanobodies® are antibody-

derived proteins developed by Ablynx which

contain novel structural and functional properties

of naturally-occurring heavy-chain antibodies

[CONT.]

Undefined mechanism

148

Research programme: muscarinic

receptor agonists - Mithridion

Mithridion (formerly Cognitive Pharmaceuticals)

in the US is developing small molecule,

muscarinic receptor agonists for the treatment of

various central nervous system (CNS) disorders,

particularly schizophrenia and associated

cognitive deficits. The muscarinic programme

was originated by the University of Toledo, which

licensed it to Cognitive Pharmaceuticals (later

Mithridion). [CONT.]

147

Research programme: monoclonal

antibodies and antibody-drug

conjugates - Intellect Neurosciences

Intellect Neurosciences is using its proprietary

Antisenilin® passive immunisation technology to

develop monoclonal antibodies that target beta-

amyloid (Abeta) protein for the treatment of

Alzheimer's disease (AD). The company licensed

two Abeta-specific monoclonal antibodies, 82E1

(IN N01) and 1A10, from Immuno-Biological

Laboratories (IBL). [CONT.]

146

Research programme: metal-protein-

attenuating compounds - Prana

Biotechnology

Prana Biotechnology is undertaking a research

programme to develop disease-modifying agents

derived from its proprietary metal-protein-

attenuating compound (MPAC) library for the

treatment of Alzheimer's disease, Parkinson's

disease (PD), and possibly age-related macular

degeneration (AMD). [CONT.]

144

Research programme: membrane

active metal ion chelators - D-Pharm

Chelating agents

145

Research programme: metabotropic

glutamate receptor 5 modulators -

Addex Therapeutics

Addex Therapeutics (formerly Addex

Pharmaceuticals) is evaluating positive and

negative allosteric metabotropic glutamate

receptor-5 (mGluR5) modulators for potential

application in schizophrenia, Alzheimer's disease

and other cognitive disorders. Allosteric

modulators are a novel class of small-molecule,

oral drug candidates with a chemical structure

unrelated to that of competitive agonist or

antagonist drugs [CONT.]

Metabotropic glutamate receptor 5 modulators

143

Research programme:

melanotransferrin conjugated

therapeutics - biOasis Technologies

biOasis Technologies is developing

melanotransferrin (p97; CD228) as a carrier of

therapeutic and imaging agents across the blood-

brain barrier (BBB) for use in various indications,

including brain metastases and Alzheimer's

disease. A melanotransferrin-trastuzumab

(Herceptin®) conjugate, known as BT 2111, is

undergoing preclinical studies for the treatment

of HER2+ brain cancer that has metastasised

from primary breast cancer, in Canada [CONT.]

Liver X receptor modulators

142

Research programme: M1 muscarinic

receptor modulators - Merck and Co.

Merck & Co. is developing selective M1

muscarinic positive allosteric receptor


disease. Development of the programme is at the


Muscarinic M1 receptor modulators

140

Research programme: leptin -

Neurotez

Neurotez is developing a hormone product

candidate leptin for the treatment of Alzheimer's

disease (AD) and other cognitive disorders.

Leptin is a protein that is derived from adipocyte

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

phosphorylation. [CONT.]

Leptin - Neurotez

141

Research programme: liver X

receptor modulators - Vitae

Pharmaceuticals

Vitae Pharmaceuticals is developing small

molecule liver X receptor (LXR) modulators for

the treatment of atherosclerosis and Alzheimer's

disease. Discovery is based on Vitae's

CONTOUR® technology, a structure-based drug

design platform which allows design and

optimisation of compounds within the binding site

of a target protein. [CONT.]

139

Research programme: kinase

inhibitors - Plexxikon

Plexxikon (a Daiichi Sankyo subsidiary) is

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)

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.]

NNI-370

PYM 60086 Alzheimer's disease Preclinical PO United Kingdom Phytopharm Originator England Pharmaceutical Public

PYM60086 Cognition disorders Preclinical PO United Kingdom Phytopharm Owner England Pharmaceutical Public

Dementia Preclinical PO United Kingdom

Memory disorders Preclinical PO China

DP 68 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Intranasal USA ProteoTech Originator USA Biotechnology Private

DP 74 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical PO USA ProteoTech Owner USA Biotechnology Private

DP-68 Parkinson's disease Preclinical PO USA

DP-74

PeptiClere™

PTI 777

PTI-777

Synuclere™

TTT 3002 LRRK2 protein inhibitors Alzheimer's disease Preclinical PO USA TauTaTis Originator USA Pharmaceutical Private

TTT-3002 Protein kinase inhibitors Cancer Preclinical PO USA TauTaTis Owner USA Pharmaceutical Private

Tau protein modulators Parkinson's disease Preclinical PO USA

Alzheimer's disease Preclinical Unknown route Sweden BioChromix Pharma Originator Sweden Pharmaceutical Private

BioChromix Pharma Owner Sweden Pharmaceutical Private

Alzheimer's disease Preclinical Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

Neurodegenerative disorders Preclinical Unknown route USA KineMed Originator USA Biotechnology Private

ORY 2001 Lysine specific demethylase 1 modulators Huntington's disease Preclinical Unknown route Spain Oryzon Originator Spain Biotechnology Private

ORY-2001 Monoamine oxidase B inhibitors Alzheimer's disease Research Unknown route Spain Oryzon Owner Spain Biotechnology Private

Dementia Research Unknown route Spain

Parkinson's disease Research Unknown route Spain

PharmaNeuroBoost N.V. of Belgium is

undertaking a research programme to develop

compounds for the treatment of

neurodegenerative disorders, particularly

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

(PD). Lead candidates are undergoing preclinical

development for AD and PD.

PNB 03 Alzheimer's disease Preclinical Unknown route Belgium PharmaNeuroBoost Originator Belgium Pharmaceutical Private

Two lead candidates to emerge is PNB 03 and

PNB 04, which are undergoing IND-enabling

studies for PD and AD, respectively.

PNB 04 Parkinson's disease Preclinical Unknown route Belgium PharmaNeuroBoost Owner Belgium Pharmaceutical Private

PNB03

PNB04

Caprospinol Acetylcholinesterase inhibitors Alzheimer's disease Preclinical PO Canada Advinus Therapeutics Collaborator India CRO Private

SP 04 Amyloid beta-protein inhibitors Huntington's disease Preclinical PO USA CHDI Collaborator USA Biotechnology Private

SP 04m Sigma-1 receptor antagonists Georgetown University Originator USA University N/A

SP 08 McGill University Originator Canada University N/A

SP 233 Samaritan Pharmaceuticals Originator USA Biopharmaceutical Public

SP-004

SP-008

SP-04

SP-04m

SP-08

SP-233

sNN 0126 Neuron stimulants Alzheimer's disease Preclinical Unknown route Sweden Genentech Technology Provider USA Large Pharma, Biotechnology Public

sNN 0465 Neuropilin-1 inhibitors Amyotrophic lateral sclerosis Preclinical Intracerebro ventricular Sweden NeuroNova AB Originator Sweden Biopharmaceutical Private

sNN0126 Platelet derived growth factor BB modulators Huntington's disease Preclinical Unknown route Sweden NeuroNova AB Owner Sweden Biopharmaceutical Private

sNN0465 Stem cell stimulants Major depressive disorder Preclinical Unknown route Sweden

Neurological disorders Preclinical Intracerebro ventricular Sweden

Neurological disorders Preclinical PO Sweden

Parkinson's disease Preclinical Intracerebro ventricular Sweden

AF 243 Cell differentiation stimulants Hearing loss Preclinical Otic France Affichem Originator France Biotechnology Private

AF 250s Neuron modulators Parkinson's disease Preclinical Unknown route France Affichem Owner France Biotechnology Private

AF243 Alzheimer's disease Research Unknown route France

AF250s Brain injuries Research Unknown route France

Retinal disorders Research Ophthalmic France

Alzheimer's disease Preclinical Unknown route Australia Neurosciences Victoria Originator Australia Technology Transfer Private

Amyotrophic lateral sclerosis Preclinical Unknown route Australia Neurosciences Victoria Owner Australia Technology Transfer Private

Epilepsy Preclinical Unknown route Australia

Multiple sclerosis Preclinical Unknown route Australia

Neurological disorders Preclinical Unknown route Australia

Parkinson's disease Preclinical Unknown route Australia

Stroke Preclinical Unknown route Australia

ORS 1006 DYRK kinase inhibitors Alzheimer's disease Preclinical PO USA Arrien Pharmaceuticals Collaborator USA Pharmaceutical Private

ORS 1104 LRRK2 protein inhibitors Down syndrome Preclinical PO USA Oros Pharmaceuticals Originator India Manufacturer

ORS-1006 Parkinson's disease Preclinical PO USA Oros Pharmaceuticals Owner India Manufacturer

ORS-1104

162

Research programme: neurological

disorders kinase inhibitors - Arrien

Pharmaceuticals

Arrien Pharmaceuticals is developing orally

administered, small molecule inhibitors of protein

kinases for the treatment of Alzheimer's disease

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

syndrome. These compounds were originated by

Oros Pharmaceuticals, and are being developed

with Arrien's proprietary Fragment-Field Drug

Design (FFDD)™ technology platform. [CONT.]

161


disorder therapies - Neurosciences

Victoria

Australia-based Neurosciences Victoria is

conducting research into several neurological

disorders, with the aim of discovering potential

therapeutics. The company's areas of research

include epilepsy, stroke, neurodegenerative

disorders, primarily Alzheimer's disease,

Parkinson's disease and amyotrophic lateral

sclerosis, and glial cell disorders, particularly

multiple sclerosis (MS). [CONT.]

Undefined mechanism

160


disorder therapeutics - Affichem

Affichem is developing therapeutics for disorders

with neurological involvement including; hearing

loss, Parkinson's disease, Alzheimer's disease,

retinal disorders (retinopathy) and medullary

lesions. A lead candidate, AF 243, is undergoing

preclinical development. Early research is also

being conducted on another candidate known as

AF 250s. [CONT.]

159

Research programme: neurogenesis

therapeutics - NeuroNova AB

NeuroNova AB is engaged in the discovery and

development of small molecule drugs that

promote neurogenesis (i.e. the formation of new

neurons) via activity on neural stem and

progenitor cells for the treatment of CNS

disorders, including Parkinson's disease (PD),

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

(HD), amyotrophic lateral sclerosis (ALS) and

depression. [CONT.]

158

Research programme:

neurodegenerative disorders

therapeutics - Samaritan/McGill

University

The US company Samaritan Pharmaceuticals is

collaborating with McGill University in Canada in

the discovery and development of therapeutics

for the treatment of neurodegenerative disorders

such as Alzheimer's disease (AD) and

Huntington's disease (HD). Certain compounds in

this programme (such as caprospinol) inhibit

beta-amyloid and others (such as SP 04) inhibit

acetylcholinesterase and the sigma-1 receptor

[CONT.]

156

Research programme:


therapeutics - Oryzon

Oryzon is developing small molecule therapeutics

for the treatment of neurodegenerative disorders,

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

disease (PD), dementia, and Huntington's

disease (HD). The research programme focuses

on targeting lysine specific demethylase 1

(LSD1), which plays a role in regulating the

expression of crucial genes that support neuron

viability. [CONT.]

157

Research programme:


therapeutics - PharmaNeuroBoost

154

Research programme:


therapeutics - BioChromix Pharma

BioChromix Pharma has a research programme

investigating therapeutics for the treatment of

neurodegenerative disorders. The company's

initial focus is on Alzheimer's disease. Lead

compounds based on proprietary polymer

technology are in preclinical investigation.

155

Research programme:


therapeutics - KineMed/Bristol-

Myers Squibb

KineMed and Bristol-Myers Squibb are developing


disease and other neurodegenerative disorders.

KineMed will utilise their stable isotope

technology to aid in drug discovery. Preclinical


Undefined mechanism

153

Research programme:

neurodegenerative disorder

therapeutics - TauTaTis

TauTaTis is undertaking a research programme

to discover and develop a series of proprietary

and orally bioavailable, small molecules as multi-

targeted kinase inhibitors for the treatment of

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

(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

symptomatic relief [CONT.]

152

Research programme:


therapeutics - ProteoTech

ProteoTech is developing proprietary, small

molecules for the potential use in

neurodegenerative disorders such as Alzheimer's

disease (AD) and Parkinson's disease (PD). Drug

classes that have emerged from this programme

include small molecules and peptides that reduce

and/or trigger clearance of amyloid-beta (Abeta)

for AD and molecules targeting the formation and

persistence of alpha-synuclein in PD [CONT.]

151

Research programme:


therapeutics - Phytopharm

UK-based pharmaceutical company Phytopharm

is developing botanical-based pharmaceuticals

for the treatment of dementia including

Alzheimer's disease (programme P58),

Parkinson's disease (programme P63), vascular

dementia and age-related memory impairment.

Additional indications include diabetic neuropathy

and neuropsychiatric disorders, such as

schizophrenia, depression, anxiety and epilepsy.

[CONT.]

Nerve growth factor stimulants

150

Research programme:


therapeutics - Neuronascent

Neuronascent is developing a series of chemically

diverse neurogenic compounds as disease-

modifying drugs for the treatment of

neurodegenerative diseases including Alzheimer's

disease (AD) and Parkinson's disease. The

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.]

SP sc4 Alzheimer's disease Preclinical Unknown route Canada CHDI Licensee World Biotechnology Private

SP sc7 Huntington's disease Preclinical Unknown route USA Georgetown University Originator USA University N/A

SP-sc4 Neurodegenerative disorders Preclinical Unknown route Canada McGill University Originator Canada University N/A

SP-sc7 Samaritan Pharmaceuticals Originator USA Biopharmaceutical Public

BN 201 TrkA receptor agonists Glaucoma Preclinical Ophthalmic Spain Bionure Originator Spain Biotechnology Private

BN-201 TrkB receptor agonists Multiple sclerosis Preclinical IV Spain Bionure Owner Spain Biotechnology Private

BN201 Multiple sclerosis Preclinical PO Spain

G 79 Optic neuritis Preclinical IV Spain

G-79 Alzheimer's disease Research IV Spain

G79 Amyotrophic lateral sclerosis Research IV Spain

Parkinson's disease Research IV Spain

ADNF-9 Neuron stimulants Alzheimer's disease Preclinical Unknown route Canada Allon Therapeutics Originator Canada Biotechnology Public

AL 209 Tubulin modulators Fetal alcohol syndrome Preclinical Unknown route Canada Paladin Labs Owner Canada Pharmaceutical Public

AL 309 Neuroprotection Preclinical PO USA

AL 408 Peripheral nervous system diseases Preclinical PO Canada

AL 508 Peripheral nervous system diseases Preclinical SC Canada

AL-209 Peripheral nervous system diseases (Chemotherapy-

induced:oxaliplatin induced peripheral neuropathy)

Preclinical PO France

AL-309 Eye disorders No development reported(Preclinical) Unknown route Germany, Israel

AL-408

AL-508

SAL

SALLRSIPA

Alzheimer's disease Preclinical Intranasal Italy Lay Line Genomics Originator Italy Biopharmaceutical Private

Lay Line Genomics Owner Italy Biopharmaceutical Private

NRX 1050 Alzheimer's disease Preclinical PO USA Naurex Originator USA Biopharmaceutical Private

NRX 1051 Autistic disorder Preclinical PO USA Naurex Owner USA Biopharmaceutical Private

NRX 1059 Major depressive disorder Preclinical IV USA

NRX 105x Major depressive disorder Preclinical PO USA

NRX 1060 Neuropathic pain Preclinical PO USA

NRX 2085 Schizophrenia Preclinical IV USA

NRX 20xx Schizophrenia Preclinical PO USA

NRX-1050

NRX-1051

NRX-1059

NRX-105x

NRX-1060

NRX-2085

NRX-20xx

AD Inov collaborative programme Cytoplasmic and nuclear receptor modulators Alzheimer's disease Preclinical Unknown route France Genfit Originator France Biopharmaceutical Public

G-15750 Nuclear receptor subfamily 1 group F member 3

antagonists

Cardiovascular disorders Preclinical Unknown route France Genfit Owner France Biopharmaceutical Public

G15750 Peroxisome proliferator-activated receptor

modulators

Metabolic disorders Preclinical Unknown route France

TGFTX1 Autoimmune disorders Research Unknown route France

TGFTX3

RAP 103 CCR2 receptor antagonists Alzheimer's disease Preclinical PO USA McGill University Collaborator Canada University N/A

RAP 160 CCR3 receptor antagonists Hepatitis B Preclinical PO Germany, USA RAPID Pharmaceuticals Originator Switzerland Biotechnology Private

RAP 163 CCR5 receptor antagonists Neuropathic pain Preclinical PO Canada, USA RAPID Pharmaceuticals Owner Switzerland Biotechnology Private

RAP 164 Chemokine receptor antagonists Prostate cancer Preclinical PO USA University of Duisburg-Essen Collaborator Germany University N/A

RAP 310 Chemokine receptor modulators Psoriasis Preclinical PO USA University of Michigan Collaborator USA University N/A

RAP 701 Immunostimulants Ovarian cancer Research PO USA

RAP103 Stem cell inhibitors

RAP160

RAP163

RAP164

RAP310

RAP701

[18F]AppCHFppA Atherosclerosis (Diagnosis) Preclinical Parenteral USA FluoroPharma Licensee USA Biopharmaceutical Private

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

GSK3787 Alzheimer's disease Preclinical PO USA GlaxoSmithKline Originator England Large Pharma, Pharmaceutical Public

GW 0742 Cancer Preclinical Unknown route USA GlaxoSmithKline Owner England Large Pharma, Pharmaceutical Public

GW0742 Diabetes mellitus Preclinical Unknown route USA

PPAR agonists research programme -

GlaxoSmithKline

Lipid metabolism disorders No development reported(Preclinical) Unknown route USA

PPARpan Metabolic syndrome No development reported(Preclinical) Unknown route USA

PPARpan™

Research programme: PPARpan agonists -

GlaxoSmithKlineND 602 Alzheimer's disease Preclinical Unknown route Canada Neurodyn Originator Canada Biotechnology

ND-602 Amyotrophic lateral sclerosis Preclinical Unknown route Canada Neurodyn Owner Canada Biotechnology

Parkinson's disease Preclinical Unknown route Canada

Spinal muscular atrophy Preclinical Unknown route Canada

NPT 001 Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral USA NeuroPhage Pharmaceuticals Originator USA Biotechnology

NPT 002 - NeuroPhage Amyloid beta-protein inhibitors Parkinson's disease Preclinical Unknown route USA NeuroPhage Pharmaceuticals Owner USA Biotechnology

NPT-001 Tau protein inhibitors

NPT-002 - NeuroPhage

NPT001

NPT002 - NeuroPhage

173

Research programme: protein

aggregation inhibitors - NeuroPhage

Pharmaceuticals

NeuroPhage Pharmaceuticals is developing


neurodegenerative disease, including Alzheimer's

disease and Parkinson's disease. The company is

using its proprietary protein disaggregation

technology targeting both beta-amyloid (Abeta)

and tau proteins as a disease-modifying

approach in the treatment of Alzheimer's disease.

[CONT.]

172

Research programme: progranulin

stimulants - Neurodyn

Neurodyn is developing a neuroprotectant, called

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

synthesis of progranulin, a multifunction protein

expressed by neurons and microglia. Progranulin

is thought to be involved in neuronal survival and

CNS inflammatory processes [CONT.]

Nerve tissue protein stimulants

170

Research programme: PET imaging

agents - FluoroPharma

FluoroPharma is developing positron emission

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

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.]

Positron-emission tomography enhancers

171

Research programme: PPAR

modulators - GlaxoSmithKline

GlaxoSmithKline is developing modulators for the

three known peroxisome proliferator-activated

receptor (PPAR) subtypes alpha, gamma and

delta, for the potential treatment of cancer, type

2 diabetes and Alzheimer's disease (AD).

Preclinical studies of a series of compounds are

underway in the US. A PPARdelta agonist, GW

0742, has been tested in a mice model of AD. A

PPAR beta/delta antagonist, GSK 3787, has also

been evaluated in the treatment of cancer.

[CONT.]

Peroxisome proliferator-activated receptor

modulators

169

Research programme: peptide-based

therapeutics - RAPID

Pharmaceuticals

RAPID Pharmaceuticals is developing small

stable peptides for the treatment of Alzheimer's

disease (RAP 310), chronic hepatitis B (RAP

164), neuropathic pain (RAP 103), ovarian

cancer (RAP 701), prostate cancer (RAP 163)

and psoriasis (RAP 160). The company has

stated that these compounds, which target

specific chemokine receptors, represent a fourth

generation of peptide development. [CONT.]

168

Research programme: nuclear

receptor-targeting therapeutics -

Genfit

Genfit is developing compounds that target

various nuclear receptors for the treatment of

Alzheimer's disease, cardiometabolic disorders

and autoimmune disorders. Drug candidates

include G 15750, a selective peroxisome

proliferator-activated receptor modulator. Genfit

has two programmes, TGFTX1 and TGFTX3,

which target nuclear receptors that are involved

in the circadian rhythm (Rev-Erbalpha and

RORalpha/RORgamma) [CONT.]

166

Research programme: NGF-based

Alzheimer's disease therapy - Lay

Line Genomics

Lay Line Genomics is developing proprietary

formulations of nerve growth factor (NGF)

coupled to a diagnostic system for the non-

invasive treatment of Alzheimer's disease. An

intranasal formulation of NGF is undergoing proof-

of-principle, preclinical studies in Italy. [CONT.]

Neuron stimulants

167

Research programme: NMDA

receptor modulators - Naurex

Naurex is developing peptides and synthetic

small molecules as modulators of the N-methyl-D-

aspartate (NMDA) receptor for the treatment of

major depressive disorder, schizophrenia,

Alzheimer's disease, neuropathic pain and

autistic disorder. In preclinical trials, NMDA

modulators have exhibited therapeutic activity

without the limiting side effects, such as

dissociative effects and sedation, commonly

observed with other compounds targeting the

NMDA receptor [CONT.]

NMDA receptor modulators

165

Research programme:

neuroprotective therapies - Allon

Therapeutics

Allon Therapeutics (a subsidiary of Paladin Labs)

has a research programme aimed at developing

neuroprotective compounds derived from its two

technology platforms, Activity-Dependent

Neurotrophic Factor (ADNF) and Activity-

Dependent Neuroprotective Protein (ADNP), for

the treatment of degenerative diseases and

injuries. [CONT.]

164

Research programme:

neuroprotectants - Bionure

Bionure is developing neuroprotectants for the

treatment of neurological and ophthalmological

indications, including multiple sclerosis,

Parkinson's disease, Alzheimer's disease,

glaucoma and acute optic neuritis. A lead

candidate from this programme is BN 201 (also

known as G 79), a first-in-class peptoid

neuroprotectant that works by binding to the

extracellular portion of TrkA and TrkB and

activating the neurotrophin pathway [CONT.]

163

Research programme: neuronal stem

cell therapeutics - Samaritan/McGill

University

Samaritan Pharmaceuticals in the US is

collaborating with McGill University in Canada in

the discovery and development of small molecule

compounds that induce neural stem cell

differentiation, as potential treatments of various

neurodegenerative disorders. [CONT.]

Stem cell stimulants

Alpha-synuclein inhibitors Alzheimer's disease Preclinical Parenteral Ireland Neotope Biosciences Originator United Kingdom Biopharmaceutical Public

Amyloid inhibitors Amyloidosis Preclinical Parenteral Ireland Prothena Corporation Owner Ireland Biotechnology Public

Protein aggregation inhibitors Neurodegenerative disorders Preclinical Parenteral Ireland

Tau protein inhibitors Parkinson's disease Preclinical Parenteral Ireland

SIG 1012 Alzheimer's disease Preclinical PO USA GlaxoSmithKline (China) Investment Co. Licensee China Pharmaceutical Public

SIG 1106 Parkinson's disease Research PO USA Princeton University Technology Provider USA University N/A

SIG1012 Type 2 diabetes mellitus Research PO USA Signum Biosciences Originator USA Biotechnology Private

SIG1033 Signum Biosciences Owner USA Biotechnology Private

SIG1106

A 992400 Alzheimer's disease Preclinical Parenteral Germany Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

A 992401 AbbVie Owner USA Biopharmaceutical Public

A-992400 CSL Behring Originator USA Biopharmaceutical Public

A-992401 CSL Behring Owner USA Biopharmaceutical Public

EHT 0101 Amyloid beta-protein inhibitors Alzheimer's disease Preclinical Unknown route France ExonHit Therapeutics Originator France Technology provider Public

EHT 0206 GTP phosphohydrolase inhibitors Cancer Preclinical Unknown route France ExonHit Therapeutics Owner France Technology provider Public

EHT 101 Ras signal transduction pathway inhibitors Chronic myeloid leukaemia Preclinical Unknown route France

EHT 1864 Rho GTP-binding protein-inhibitors

EHT 206

Acetylcholinesterase inhibitors Alzheimer's disease Preclinical Transdermal South Korea Samyang Biopharmaceuticals Corporation Originator South Korea Pharmaceutical

Butyrylcholinesterase inhibitors Samyang Group Originator South Korea Pharmaceutical Public

Merck & Co is developing orally bioavailable S-

adenosylhomocysteine hydrolase (AHCY)


disease. Development is at the preclinical stage

in the US.

L 002259713 Alzheimer's disease Preclinical PO USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Homocysteine is produced by the conversion of S-

adenosylhomocysteine via the AHCY cytosolic

enzyme to homocysteine and adenosine. [CONT.]

L-002259713 Merck & Co Owner USA Large Pharma, Pharmaceutical Public

SUVN-F90101 Alzheimer's disease Preclinical Unknown route India Suven Life Sciences Originator India Company

SUVN-F91201 Neuropathic pain Preclinical Unknown route India Suven Life Sciences Owner India Company

Alzheimer's disease Preclinical Unknown route USA Abide Therapeutics Originator USA Biotechnology Private

Down syndrome Preclinical Unknown route USA University of California, San Diego Originator USA University N/A

SUVN D1003019 Alzheimer's disease Preclinical PO India Suven Life Sciences Originator India Company

SUVN-D1003019 Suven Life Sciences Owner India Company

A 964324 Alzheimer's disease Preclinical Unknown route USA Abbott Laboratories Originator USA Large Pharma, Pharmaceutical Public

A-964324 Schizophrenia Preclinical Unknown route USA AbbVie Owner USA Biopharmaceutical Public

A964324

SUVN-501 Alzheimer's disease Preclinical PO India Suven Life Sciences Originator India Company

SUVN-504 Cognition disorders Preclinical PO India Suven Life Sciences Owner India Company

SUVN-507 Obesity Preclinical PO India

SUVN-623 Parkinson's disease Preclinical PO India

SUVN-901 Schizophrenia Preclinical PO India

SUVN-976

321348 Alzheimer's disease Preclinical PO USA Pfizer Owner USA Large Pharma, Pharmaceutical Public

5-HT6 receptor antagonists - Wyeth Wyeth Originator USA Large Pharma, Pharmaceutical Public

WAY 101

WAY-101

185

Research programme: serotonin 6

receptor antagonists - Wyeth

Wyeth (Pfizer) is developing serotonin 6 (5-HT6)

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

learning and memory by increasing levels of the

neurotransmitters acetylcholine and glutamate. A

series of arylsulfonyl compounds has been

developed with optimised pharmacodynamic

properties [CONT.]


184


receptor antagonists - Suven Life

Sciences

Suven Life Sciences is developing orally active,

selective serotonin 6 (5-HT6) receptor

antagonists, including tetrahydro carbazole

derivatives, for the treatment of various cognition

disorders such as Alzheimer's disease and

schizophrenia, as well as obesity. SUVN 501,

SUVN 504, SUVN 507 (and its active metabolite,

M1), SUVN 901 and SUVN 976 are in preclinical

development in India. [CONT.]


183


receptor antagonists - AbbVie

AbbVie (formerly Abbott laboratories) is

researching serotonin-6 (5HT6) receptor

antagonists for their potential in the treatment of

cognitive deficits in Alzheimer's disease and

schizophrenia in the US. Lead candidate A

964324 is a highly selective serotonin-6 receptor

antagonist in in vitro and in vivo studies.

Preclinical development is ongoing in the US.

[CONT.]


181

Research programme: serine

hydrolase inhibitors - Abide

Therapeutics/University of California

Abide Therapeutics and the University of

California, San Diego are collaborating on the

development of small-molecule inhibitors of

monoacylglycerol lipase (MAGL), a serine

hydrolase, as potential therapies for Down

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.]

Hydrolase inhibitors

182


receptor agonists - Suven Life

Sciences

Suven Life Sciences is developing orally

bioavailable, selective serotonin 4 receptor

(5HT4) agonists for the treatment of Alzheimer's

disease. 5-HT4 receptor is expressed at a high

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.]

Serotonin 4 receptor agonists

179

Research programme: S-

adenosylhomocysteine hydrolase

inhibitors - Merck & Co

Adenosylhomocysteinase inhibitors

180

Research programme: selective


agonists - Suven Life Sciences

Suven Life Sciences is developing potent and

selective nicotinic acetylcholine alpha4beta2

receptor agonists for the treatment of

neurological disorders. SUVN F91201 has been

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.

Nicotinic receptor agonists

178

Research programme: rivastigmine

transdermal - Samyang

A transdermal formulation of rivastigmine is

being developed by Samyang Biopharmaceuticals

Corporation (a division of Samyang Group) for

the treatment of Alzheimer's disease. The

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.]

176

Research programme: RAGE

monoclonal antibodies: AbbVie/CSL

Behring

AbbVie and CSL Behring are developing

monoclonal antibodies (mABs) to receptor for

advanced glycation-end-products (RAGE) for the

treatment of Alzheimer's disease (AD). RAGE is

thought to be a receptor for amyloid-beta

(Abeta) and other ligands such as S100B,

potentially contributing to AD disease

progression. It is overexpressed in the brain

microvasculature of patients with AD. [CONT.]


antagonists

177

Research programme: Rho GTP-

binding protein inhibitors - ExonHit

Therapeutics

ExonHit Therapeutics is utilising its Differential

Analysis of Transcripts with Alternative Splicing

(DATAS™) technology to develop small molecule

inhibitors of rho GTP-binding proteins (GTPases)

for the treatment of cancer and Alzheimer's

disease. Rho GTP-binding proteins are involved in

regulation of actin organisation, gene expression

and cell cycle expression. Preclinical studies are

being conducted by ExonHit in France. [CONT.]

175


phosphatase 2A modulators -

GlaxoSmithKline/Signum

Biosciences

Signum Biosciences is using its proprietary

Phosphatase plaform to develop small molecule,

orally active protein phosphatase 2A (PP2A)


disease, Parkinson's disease, and type 2 diabetes

mellitus. GlaxoSmithKline (China) is collaborating

with Signum on the research and development in



Protein phosphatase 2A modulators

174


aggregation inhibitors - Prothena

Corporation

Neotope Biosciences (a wholly-owned subsidiary

of Elan Corporation) initiated the development of

monoclonal antibodies that modulate neo-epitope

amyloid related targets, alpha synuclein and tau

protein. These compounds could potentially be

used for the treatment of a range of

neurodegenerative disorders including primary

(AL) amyloidosis, Lewy body dementia,

Parkinson's disease and Alzheimer's disease

[CONT.]

NEOD002

Alzheimer's disease Preclinical Unknown route Scotland Antoxis Originator United Kingdom Biotechnology

Cancer Preclinical Unknown route Scotland Antoxis Owner United Kingdom Biotechnology

Cardiovascular disorders Preclinical Unknown route Scotland

Diabetes mellitus Preclinical Unknown route Scotland

Parkinson's disease Preclinical Unknown route Scotland

Cyclin dependent kinase 9 inhibitors Alzheimer's disease Preclinical PO Germany Evotec AG Collaborator Germany Pharmaceutical Public

Glutaminyl-peptide cyclotransferase inhibitors Inflammation Preclinical PO Germany Probiodrug Originator Germany Pharmaceutical Private

Probiodrug Owner Germany Pharmaceutical Private

TauRx Pharmaceuticals of Singapore is

undertaking a research programme to develop

orally available, second-generation inhibitors of

tau protein for the treatment of Alzheimer's

disease (AD). The programme is in preclinical

development.

Alzheimer's disease Preclinical PO Singapore TauRx Pharmaceuticals Originator Singapore Pharmaceutical

TauRx is pursuing commercialisation, licensing

and/or partnering opportunities for its

programme in neurodegenerative disorders,

particularly AD. [CONT.]

TauRx Pharmaceuticals Owner Singapore Pharmaceutical

HL 152B AMP activated protein kinase stimulants Age-related macular degeneration Preclinical Ophthalmic South Korea HanAll Biopharma Originator South Korea Pharmaceutical Private

HL 156Can Cell adhesion molecule inhibitors Autoimmune disorders Preclinical IV South Korea Korea Research Institute of Chemical Technology Originator South Korea Institution N/A

HL004 Emt protein-tyrosine kinase inhibitors Cancer Preclinical PO South Korea

HL010 Fc receptor antagonists Dry eyes Preclinical Ophthalmic South Korea

HL011 Gluconeogenesis inhibitors Hypertension Preclinical PO South Korea, USA

HL020 Immunomodulators Inflammatory bowel diseases Preclinical PO South Korea

HL021 Tumour necrosis factor alpha inhibitors Uveitis Preclinical Ophthalmic South Korea

HL022 Alzheimer's disease Research PO South Korea

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

HL036 (anti-TNF-alpha protein) Thrombocytopenia Research PO South Korea

HL038

HL039

HL051

HL076

HL102

HL130

HL152B

HL156

HL156Can

HL157 (oral monoclonal antibody) - HanAll

BiopharmaHL160

metformin butyrate - HanAll BioPharma

Second-generation metformin products - HanAll

BiopharmaTissue protection technology research

programme - Warren Pharmaceuticals/Lundbeck

Alzheimer's disease Preclinical Unknown route USA Asterand plc Technology Provider USA Pharmaceutical Public

Tissue-protective cytokines Neuroprotection Preclinical Unknown route USA Lundbeck A/S Collaborator World Large Pharma, Pharmaceutical Public

Warren Pharmaceuticals Originator USA Biotechnology Private

Warren Pharmaceuticals Owner USA Biotechnology Private

hUCB stem cell therapies - Saneron CCEL

Therapeutics

Amyloid beta-protein inhibitors Alzheimer's disease Preclinical IV USA Cryo-Cell International Funder USA Technology provider Public

Human umbilical cord blood stem cell therapies -

Saneron CCEL Therapeutics

Cell replacements Amyotrophic lateral sclerosis Preclinical IV USA Saneron CCEL Therapeutics Originator USA Biotechnology Private

U-CORD-CELL™ Enzyme stimulants Mucopolysaccharidosis III Preclinical IV USA Saneron CCEL Therapeutics Owner USA Biotechnology Private

Nerve growth factor stimulants Myocardial infarction Preclinical IV USA University of Minnesota Technology Provider USA University N/A

Stroke Preclinical IV USA University of South Florida Collaborator USA University N/A

Allergy vaccine - VLP Biotech Immunomodulators Hepatitis C Preclinical Unknown route USA VLP Biotech Originator USA Biotechnology Private

Alzheimer's disease vaccine - VLP Biotech Immunostimulants Influenza virus infections Preclinical Unknown route USA VLP Biotech Owner USA Biotechnology Private

Atherosclerosis vaccine - VLP Biotech Malaria Preclinical Unknown route USA

Cancer vaccine - VLP Biotech Alzheimer's disease Research Unknown route USA

Hepatitis C virus vaccine - VLP Biotech Atherosclerosis Research Unknown route USA

Hypersensitivity vaccine - VLP Biotech Cancer Research Unknown route USA

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

Immunostimulants Cancer Preclinical Unknown route USA Idera Pharmaceuticals Collaborator USA Biotechnology Public

Toll-like receptor 7 agonists Alzheimer's disease Research Unknown route USA Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Toll-like receptor 8 agonists Bacterial infections Research Unknown route USA Merck & Co Owner USA Large Pharma, Pharmaceutical Public

Toll-like receptor 9 agonists Viral infections Research Unknown route USA

Alzheimer's disease Preclinical Unknown route United Kingdom, USA Roche Originator Switzerland Large Pharma, Pharmaceutical Public

Roche Owner Switzerland Large Pharma, Pharmaceutical Public

NK 002 Alzheimer's disease Research Unknown route Canada Neurokine Pharmaceuticals Originator Canada Pharmaceutical Public

NK-002 Neurokine Pharmaceuticals Owner Canada Pharmaceutical Public

194

RO 638695 Scientists at the University College of London are

collaborating with Roche in the development of

RO 638695 for the treatment of Alzheimer's

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.

CPHPC

195

Etanercept liposomal - Neurokine

Pharmaceuticals

Neurokine Pharmaceuticals in Canada is

developing NK 002 (liposomal encapsulated

etanercept) for the treatment of Alzheimer's

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.

Tumour necrosis factor inhibitors

193

Research programme: vaccines

containing toll-like receptor agonists

- Idera/Merck

Idera Pharmaceuticals and Merck are

collaborating on the development of vaccines

containing agonists of toll-like receptors (TLRs)

7, 8 and 9 for the treatment and prevention of

cancer, infectious diseases and Alzheimer's

disease. Preclinical development is underway for

cancer, while early research activities are in

progress for infectious diseases and Alzheimer's

disease, in the US. [CONT.]

191

Research programme: umbilical cord

blood stem cell therapies - Saneron

CCEL Therapeutics

Saneron CCEL Therapeutics is collaborating with

the University of South Florida to develop human

umbilical cord blood (hUCB) stem cell therapies

based on the U-CORD-CELL™ technology

platform. The programme is focused on the early

intervention and treatment of several

neurodegenerative, cardiovascular and metabolic

disorders that lack suitable treatment options.

[CONT.]

192

Research programme: vaccines - VLP

Biotech

VLP Biotech is focusing on developing a universal

vaccine against influenza A virus strains, as well

as vaccines against malaria, hepatitis C virus,

cancer, lipid disorders (atherosclerosis and

obesity), Alzheimer's disease and various

hypersensitivities. VLP Biotech's vaccine platform

is based on virus-like particles (VLP). [CONT.]

190

Research programme: tissue

protection technology -

Lundbeck/Warren Pharmaceuticals

Warren Pharmaceuticals, is using its tissue

protection technology to develop haemopoietic

cytokines which cross the blood brain barrier, as

potential therapeutics for the treatment of tissue

injury associated with conditions such as brain

and spinal cord injuries, Alzheimer's Disease and

other neurological disorders. H. Lundbeck A/S is

collaborating with Warren in the development of

therapeutics in these neurological and pyschiatric

areas [CONT.]

189

Research programme: therapeutic

agents - HanAll Biopharma

HanAll Biopharma is a Korean-based company

that is developing therapeutic agents (oral

biopharmaceuticals and/or small molecules) for

treatment of major diseases of global

importance, such as diabetes, obesity,

cardiovascular indications (hypertension,

hyperlipidaemia, atherosclerosis, angina),

opthalmic disorders, autoimmune disorders, and

cancer. [CONT.]

187

Research programme: small

molecule therapeutics - Probiodrug

Probiodrug AG is engaged in a research

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

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

strategy in the treatment of Alzheimer's disease

[CONT.]

188

Research programme: tau protein

inhibitors - TauRx Pharmaceuticals

Tau protein inhibitors

186

Research programme: small

molecule therapeutics - Antoxis

Antoxis, an Aberdeen-based biotechnology

company, is developing small molecule flavonoid


neurodegenerative disorders, such as Parkinson's

and Alzheimer's diseases, cardiovascular

disorders, diabetes, and certain cancers.

Flavonoids are polyphenolic phytochemicals that

are found in a variety of foods and beverages.

[CONT.]

Free radical modulators

Alzheimer's disease (Diagnosis) Research Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

Bristol-Myers Squibb Owner USA Large Pharma, Biopharmaceutical Public

Alzheimer's disease (Diagnosis) Research Unknown route USA GE Healthcare Originator United Kingdom Technology provider Public

Janssen Pharmaceutica Originator Belgium Pharmaceutical Public

Alzheimer's disease Research IM USA Ichor Medical Systems Originator USA Technology provider Private

Ichor Medical Systems Technology Provider USA Technology provider Private

Institute for Molecular Medicine Originator USA Institution N/A

National Institute of Neurological Disorders and Stroke Funder USA Institution N/A

University of California at Irvine Collaborator USA University N/A

Amyloid beta-protein inhibitors Alzheimer's disease Research Parenteral Canada Cangene Corporation Originator Canada Biopharmaceutical Public

Immunomodulators Cangene Corporation Owner Canada Biopharmaceutical Public

University of British Columbia Technology Provider Canada University N/A

Alzheimer's disease Research Unknown route USA ADispell Originator USA Biotechnology Private

ADispell Owner USA Biotechnology Private

Cornell University Technology Provider USA University N/A

Alzheimer's disease Research Unknown route Japan Astellas Pharma Originator Japan Large Pharma, Pharmaceutical Public

RIKEN Originator Japan Institution N/A

Alzheimer's disease Research Unknown route USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

Penn State College of Medicine Originator USA University N/A

Alzheimer's disease Research Unknown route USA AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

The Feinstein Institute for Medical Research Collaborator USA Institution N/A

University of British Columbia Collaborator Canada University N/A

Washington University School of Medicine Collaborator USA University N/A

Weill Cornell Medical College Originator USA University N/A

Axerion Therapeutics and MedImmune, the global

biologics arm of AstraZeneca, are collaborating

to develop small and large molecules for the

treatment of Alzheimer's disease. Development is

at the research stage in the US.

Alzheimer's disease Research Unknown route USA Axerion Therapeutics Licensee USA Biotechnology Private

Both companies will work together to develop

compounds that directly block the amyloid-beta

(Abeta) oligomer binding to cellular prion

proteins in the brain. [CONT.]

MedImmune Sub-licensee USA Biotechnology Public

Yale University Originator USA University N/A

Yale University Owner USA University N/A

Alzheimer's disease Research Unknown route Italy Alzheimers Drug Discovery Foundation Collaborator USA Company

Axxam Originator Italy Biotechnology

Axxam Owner Italy Biotechnology

Alzheimer's disease Research Parenteral Sweden MIVAC Development Originator Sweden Biopharmaceutical Private

MIVAC Development Owner Sweden Biopharmaceutical Private

Alzheimer's disease Research Unknown route USA OLIGOMERIX Originator USA Biopharmaceutical Private

OLIGOMERIX Owner USA Biopharmaceutical Private

Alzheimer's disease Research Unknown route France BioSystems International Originator France Company

INSERM Originator France Institution N/A

208


disease therapeutics -

Pharnext/Biosystems

Pharnext, Biosystems International, the

University of Bordeaux Segalen and Inserm are

collaborating on a 6-year project to develop

therapeutics and diagnostics for Alzheimer's

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

diseases. [CONT.]

Undefined mechanism

206


disease therapeutics - MIVAC

Development

MIVAC Development in Sweden is developing

monoclonal antibodies for the potential treatment

of Alzheimer's disease. The company's research

is based around its discovery of methods to

engineer preparations of stabilised, highly-toxic

oligomeric amyloid-beta (Abeta). Soluble

oligomeric aggregates of the Abeta peptide are

thought to be involved in the pathogenesis of


Amyloid beta-protein modulators

207


disease therapeutics - Oligomerix

Oligomerix is developing small molecules and

antibodies that target soluble aggregates of tau

protein as a disease-modifying treatment option

for Alzheimer's disease (AD). Development is

focussed on compounds that inhibit tau oligomer

formation, disrupt tau oligomers or inhibit tau-

mediated neurotoxicity. [CONT.]


204


disease therapeutics - Axerion

Therapeutics/ MedImmune

205



Axxam/Alzheimer's Drug Discovery

Foundation

Axxam in Italy and a US-based public charity,

the Alzheimer's Drug Discovery Foundation, are

collaborating on the development of small

molecule compounds that block the purinergic

receptor P2Z (also known as P2X7) as potential

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

stage in Italy. [CONT.]

Purinoceptor P2Z antagonists

202


disease therapeutics - AstraZeneca

AstraZeneca and the University of Pennsylvania

School of Medicine are collaborating on the

development of novel therapeutics for the

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.

203



AstraZeneca/Weill Cornell Medical

College

AstraZeneca and academic research laboratories,

led by Weill Cornell Medical College, are

collaborating to assess the role of the

apolipoprotein E4 genotype (ApoE) in the

development of Alzheimer's disease and to

discover therapeutics against this target.

Development is at the research stage in the US.

Apolipoprotein E modulators

201


disease therapeutics - Astellas

Pharma/RIKEN

Astellas Pharma and RIKEN are collaborating on

the discovery and development of therapies for

Alzheimer's disease. The companies will first

identify candidate molecular targets for drug

therapy by analysis of animal models of

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.]

Undefined mechanism

200


disease therapeutics - ADispell

ADispell is developing small molecule,

neuroprotective drug candidates that target a

novel site on the nicotinic acetylcholine receptor

(nAChR) for the treatment of Alzheimer's

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

cognition disorders. [CONT.]

Nicotinic receptor modulators

198


disease DNA-vaccine - Ichor Medical

Systems

Ichor Medical Systems and the Institute for

Molecular Medicine, in the US, are developing an

intramuscular DNA-vaccine for the treatment of

Alzheimer's disease. DNA vaccine encoding

proteins, which are implicated in the development

of Alzheimer's disease, will be delivered using

Ichor's proprietary TriGrid™ electroporation

technology. This vaccine is undergoing

development in the US. [CONT.]

Immunostimulants

199


disease immunotherapy -

Cangene/University of British

Columbia

Cangene Corporation and the University of British

Columbia (UBC) are developing immune-based

therapies for the treatment of Alzheimer's

disease. Research led by an investigator at UBC

succeeded in targeting a specific epitope of

amyloid beta (Abeta) oligomers that is not

present in regular Abeta molecules. [CONT.]

196


disease diagnostic agents - Bristol-

Myers Squibb/Meso Scale Discovery

Bristol-Myers Squibb and Meso Scale Discovery

are collaborating in the development of

diagnostic assays for Alzheimer's disease (AD).

The diagnostic assays will be developed using

Meso Scale Discovery's MULTI-ARRAY®

technology platform, and will measure

cerebrospinal fluid biomarkers for use in AD

research and drug development. [CONT.]

197


disease diagnostics - GE

Healthcare/Janssed Pharmaceutica

GE Healthcare in collaboration with Janssen

Pharmaceutica N.V. is developing non-invasive or

minimally invasive diagnostic biosignatures for

pre-symptomatic detection of Alzheimer's

disease (AD). The collaboration will combine

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.]

Pharnext Originator France Biopharmaceutical

University of Bordeaux Originator France University N/A

Alzheimer's disease Research PO USA Reviva Pharmaceuticals Originator USA Pharmaceutical Private

Reviva Pharmaceuticals Owner USA Pharmaceutical Private

Alzheimer's disease Research Unknown route Sweden Umecrine Cognition Originator Sweden Pharmaceutical Private

Umecrine Cognition Owner Sweden Pharmaceutical Private

Alzheimer's disease Research Unknown route USA Yuma Therapeutics Originator USA Biopharmaceutical Private

Yuma Therapeutics Owner USA Biopharmaceutical Private

EPalpha Alzheimer's disease Research Unknown route USA Icogenex Corporation Originator USA Pharmaceutical Private

EPbeta Icogenex Corporation Owner USA Pharmaceutical Private

Alzheimer's disease Research Unknown route Japan Kyoto University Originator Japan University N/A

Shionogi Originator Japan Large Pharma, Pharmaceutical Public

Alzheimer's disease Research PO Canada, USA Alectos Therapeutics Originator Canada Biopharmaceutical Private

Merck & Co Originator USA Large Pharma, Pharmaceutical Public

Alzheimer's disease Research Unknown route Sweden AstraZeneca Originator United Kingdom Large Pharma, Pharmaceutical Public

AstraZeneca Owner United Kingdom Large Pharma, Pharmaceutical Public

Alzheimer's disease Research PO Canada Critical Outcome Technologies Originator Canada Biotechnology Private

Critical Outcome Technologies Owner Canada Biotechnology Private

Alzheimer's disease Research Unknown route USA Elan Pharmaceuticals Originator USA Biotechnology Public

Elan Pharmaceuticals Owner USA Biotechnology Public

PPD Collaborator World CRO Public

Alzheimer's disease Research Unknown route USA Biogen Idec Originator USA Large Pharma, Biotechnology Public

Multiple sclerosis Research Unknown route USA Johns Hopkins Brain Science Institute Originator USA Institution N/A

Neurodegenerative disorders Research Unknown route USA

Pain Research Unknown route USA

Medivir AB is undertaking a research programme

to develop multiple series of compounds as

inhibitors of BACE1 (beta-site amyloid precursor

protein-cleaving enzyme) for the treatment of

Alzheimer's disease (AD). Lead compounds are

undergoing optimisation in preparation for

advanced preclinical development in Sweden.

Alzheimer's disease Research Unknown route Sweden Medivir AB Originator Sweden Pharmaceutical Public

BACE1 catalyses the first step of the two-step

amyloid precursor protein (APP) cleavage

process in the brain, i [CONT.]

Medivir AB Owner Sweden Pharmaceutical Public

CATAB I - Ozgene Alzheimer's disease Research Parenteral Australia Ozgene Originator Australia Company

CATAB II - Ozgene HIV infections Research Parenteral Australia Ozgene Owner Australia Company

CATAB III - Ozgene Rheumatoid arthritis Research Parenteral Australia

CATAB IV - Ozgene

CATAB V - Ozgene

219


inhibitors - Medivir AB

Alzheimer's disease protease inhibitors - Medivir

AB


220

Research programme: catalytic

antibody therapeutics - Ozgene

Ozgene is developing catalytic antibodies for the

treatment of various diseases, including

rheumatoid arthritis, HIV infections and

Alzheimer's disease. Catalytic antibodies are

highly substrate specific and catalyse a number

of biological processes including the

actication/inactivation of proteins. Ozgene has

patented a catalytic antibody platform and early

research is ongoing in Australia. [CONT.]

Undefined mechanism

218

Research programme: analgesics and


therapies - Biogen Idec/BSi

Biogen Idec and the Johns Hopkins Brain Science

Institute (BSi) are collaborating to discover and

develop therapies for pain and for

neurodegenerative disorders such as multiple

sclerosis and Alzheimer's disease (and possibly

also Parkinson's disease). Development is at the

early research stage in the US.

BSi-Biogen Idec Research Program Undefined mechanism

216



inhibitors - Critical Outcome

Technologies

Critical Outcome Technologie (COTI) is

developing oral, small molecule inhibitors that

target amyloid precursor protein secretases (beta-

secretase and gamma-secretase) for the

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.]


217



inhibitors - Elan

Elan Pharmaceuticals, a subsidiary of Elan

Corporation, is developing small molecule

inhibitors of amyloid precursor protein secretase

(beta-secretase and gamma-secretase) for the

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

beta-amyloid (Abeta) peptides. [CONT.]

ELND007 Amyloid precursor protein secretase inhibitors

214


disease therapy - Alectos/Merck

Alectos Therapeutics in collaboration with Merck

is developing small molecule therapeutics for the

treatment of Alzheimer's disease. The

collaboration is based on Alectos' proprietary

portfolio of compounds, modulators of O-linked N-

acetylglucosaminidase (O-GlcNAcase), an

enzyme implicated in the development of


research stage in the US and Canada.

Hexosaminidase C modulators

215


derived diffusible ligand inhibitors -

AstraZeneca

AstraZeneca is developing therapeutics that

target soluble polymers (SPs) of the amyloid

beta peptide, also known as amyloid beta-

derived diffusible ligands (ADDLs), for the

potential treatment of Alzheimer's disease.

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.]

ADDL inhibitors Amyloid beta-protein inhibitors

212


disease therapies - Icogenex

Icogenex (formerly Icogen) Corporation is

developing therapeutics for the treatment of

Alzheimer's disease (AD). The company are using

its ICOCEPT™ platform to investigate

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.

[CONT.]

Amyloid beta-protein precursor modulators

213


disease therapies - Kyoto

University/Shionogi

Shionogi and Kyoto University are collaborating

on a drug discovery and medical research

project, the SK Project, to develop therapies for

Alzheimer's disease and other disorders of the

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.]

SK Project Central nervous system modulators

210


disease therapeutics - Umecrine

Cognition

Umecrine Cognition is developing compounds for

the treatment of Alzheimer's disease and

dementia. These compounds selectively modulate

the effects of GABA-steroids on GABA A

receptors in the brain. A research programme to

investigate these compounds is underway in

Sweden. [CONT.]

GABA A receptor modulators

211


disease therapeutics - Yuma

Therapeutics

Yuma Therapeutics is developing small molecule

compounds targeting tau pathway for the

treatment of Alzheimer's disease (AD). One of

the hallmarks of AD is the presence of

neurofibrillary tangles in the brains of affected

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

[CONT.]


208



Pharnext/Biosystems

Pharnext, Biosystems International, the

University of Bordeaux Segalen and Inserm are

collaborating on a 6-year project to develop

therapeutics and diagnostics for Alzheimer's

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

diseases. [CONT.]

Undefined mechanism

209


disease therapeutics - Reviva

Pharmaceuticals

Reviva Pharmaceuticals in the US is developing

orally bioavailable therapeutics for the treatment

of Alzheimer's disease. The company's internally

discovered small molecule therapeutics are

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.]

RP4000 - Reviva Pharmaceuticals Undefined mechanism

Alzheimer's disease Research PO USA National Pharmaceutical Corp Originator USA

Parkinson's disease Research PO USA Spencer Pharmaceutical Originator USA Biopharmaceutical Private

Amyloid beta-protein precursor inhibitors Alzheimer's disease Research Unknown route Belgium Galapagos NV Originator Belgium Pharmaceutical Public

G protein-coupled receptor antagonists Galapagos NV Owner Belgium Pharmaceutical Public

Alzheimer's disease Research Unknown route United Kingdom Aquapharm Biodiscovery Originator United Kingdom Biotechnology Private

University of Dundee Originator United Kingdom University N/A

Nitric oxide modulators Alzheimer's disease Research Unknown route USA NeuroMolecular Pharmaceuticals Originator USA Pharmaceutical Private

NMDA receptor antagonists Neurodegenerative disorders Research Unknown route USA NeuroMolecular Pharmaceuticals Owner USA Pharmaceutical Private

Neuropathic pain Research Unknown route USA

Alpha-synuclein inhibitors Alzheimer's disease Research Parenteral Switzerland, USA Biogen Idec Licensee World Large Pharma, Biotechnology Public

Amyloid beta-protein inhibitors Neurodegenerative disorders Research Parenteral Switzerland, USA Neurimmune Therapeutics Originator Switzerland Biotechnology Private

Tau protein inhibitors Neurimmune Therapeutics Owner Switzerland Biotechnology Private

TDP-43 protein inhibitors

Aurogen is developing therapeutics for the

treatment of neurodegenerative diseases,

including diabetic neuropathy and Alzheimer's

disease. Development is at the early research

stage in the US.

Alzheimer's disease Research Parenteral USA Aurogen Originator USA Biotechnology Private

The company's proprietary technology is based

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.]

Diabetic neuropathies Research Parenteral USA Aurogen Owner USA Biotechnology Private

Protein aggregation modulators Alzheimer's disease Research Unknown route United Kingdom Prothena Corporation Originator Ireland Pharmaceutical Public

Protein conformation modulators Parkinson's disease Research Unknown route United Kingdom University of Cambridge Originator United Kingdom University N/A

Protein folding modulators

Alzheimer's disease Research Unknown route USA Afraxis Originator USA Biotechnology Private

CNS disorders Research Unknown route USA Afraxis Owner USA Biotechnology Private

Schizophrenia Research Unknown route USA Genentech Licensee World Large Pharma, Biotechnology Public

Alzheimer's disease Research Unknown route USA PharmatrophiX Originator USA Biotechnology Private

PharmatrophiX Owner USA Biotechnology Private

Protein folding modulators - Reata

Pharmaceuticals

Alpha-synuclein inhibitors Alzheimer's disease Research PO USA Reata Pharmaceuticals Originator USA Biopharmaceutical Private

Protein misfolding reagents for

neurodegenerative diseases - Reata

Pharmaceuticals

Amyloid beta-protein inhibitors Amyotrophic lateral sclerosis Research PO USA Reata Pharmaceuticals Owner USA Biopharmaceutical Private

RTA 801 Protein folding modulators Huntington's disease Research PO USA

SOD1 reactivators - Reata Pharmaceuticals Superoxide dismutase stimulants Parkinson's disease Research PO USA

SOD1 stabilisers - Reata Pharmaceuticals

Alpha 2c adrenergic receptor antagonists Alzheimer's disease Research Unknown route Finland Orion Originator Finland Pharmaceutical Public

Undefined mechanism Schizophrenia Research IV Finland Orion Owner Finland Pharmaceutical Public

NMDA receptor modulators Alzheimer's disease Research Unknown route USA Jubilant Pharmaceuticals Collaborator USA Pharmaceutical

232

Research programme: subtype-

selective NMDA receptor modulators -

Mnemosyne Pharmaceuticals

Mnemosyne Pharmaceuticals is developing small

molecule therapeutics that target and modulate

the specific NMDA receptor subtypes of the

receptor subunit, NR2, as potential treatment for

cognitive and neuropsychiatric disorders.

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.]

231

Research programme: schizophrenia

and Alzheimer's disease therapeutics

- Orion Pharma

Orion Pharma in Finland is researching

compounds for the potential treatment of

schizophrenia and Alzheimer's disease. Three

lead compounds emerged from this programme,

ORM 14540, ORM 10921, and ORM 12741 [see

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.]

ORM-14540

229

Research programme: p75 ligands -

PharmatrophiX

PharmatrophiX in the US is developing small

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

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.]


230

Research programme: protein folding

modulators - Reata Pharmaceuticals

Reata Pharmaceuticals is developing small

molecule, protein folding modulators for the

treatment of various genetic diseases caused by

misfolded proteins. Defects in protein folding

underlie a large number of diseases including

cancer, amyotrophic lateral sclerosis (ALS),

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

(PD), cystic fibrosis, and Huntington's disease

(HD). [CONT.]

228

Research programme:

neuropsychotherapeutics - Afraxis

Afraxis is developing inhibitors of p21-activated

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

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

[CONT.]

P21 activated kinase inhibitors

226

Research programme:


therapeutics - Aurogen

Insulin-like growth factor I stimulants

227

Research programme:

neurodegenerative therapeutics -

Prothena Corporation/The University

of Cambridge

Prothena Corporation (originally Elan

Corporation) and The University of Cambridge

are collaborating to develop treatments for

Alzheimer's disease and Parkinson's disease. The

goal of the collaboration is to discover novel

compounds that can alter the molecular

behaviour of proteins (i.e folding, misfolding,

aggregation and turnover) associated with these

neurodegenerative disorders. [CONT.]

225

Research programme:


therapeutics - Biogen

Idec/Neurimmune Therapeutics

Biogen Idec and Neurimmune Therapeutics are

collaboratively developing fully human antibodies

for the treatment of neurodegenerative diseases.

The alliance will focus on the development of

antibodies that bind to amyloid beta (Abeta),

alpha-synuclein, tau, and TDP-43. These targets

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

sclerosis (ALS). [CONT.]

Hexosaminidase C inhibitors

224

Research programme: memantine

derivatives - NeuroMolecular

Pharmaceuticals

NeuroMolecular Pharmaceuticals is undertaking a

research programme to develop a series of

memantine derivatives with enhanced efficacy

and improved tolerability for the treatment of

neurodegenerative disorders such as Alzheimer's

disease (AD) and neuropathic pain. Development

is at the early research stage in the US. [CONT.]

Memantine analogues - NeuroMolecular

222

Research programme: G-protein

coupled receptor 3 antagonists -

Galapagos

Galapagos NV is undertaking a research

programme focussed on the development of

small molecule drugs that target and inhibit the

orphan G-protein coupled receptor 3 (GPR3) for

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.]

GPR3 inhibitors programme

223

Research programme:

hexosaminidase-C-inhibitors -

Aquapharm Biodiscovery/University

of Dundee

Aquapharm Biodiscovery and the University of

Dundee are developing hexosaminidase-C

inhibitors (O-GlcNAcase inhibitors) for the

treatment of Alzheimer's disease.

Hexosaminidase-C modulates the solubility of the

proteins in the aggregates associated with the

progressive neurodegeneration of Alzheimer's

disease. The compounds being investigated are

derived from Aquapharm's marine microbial

collection [CONT.]

221


therapeutics - National

Pharmaceutical/Spencer

Pharmaceutical

Spencer Pharmaceutical and National

Pharmaceutical are collaborating to develop

orally available prodrugs to treat central nervous

system (CNS) disorders, with particular focus on

Alzheimer's and Parkinson's disease. Using

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.]

Undefined mechanism

NR2B N-Methyl D-Aspartate receptor modulators Attention-deficit hyperactivity disorder Research Unknown route USA Mnemosyne Pharmaceuticals Originator USA Biotechnology Private

Brain injuries Research Unknown route USA Mnemosyne Pharmaceuticals Owner USA Biotechnology Private

Schizophrenia Research Unknown route USA

Stroke Research Unknown route USA

IMD2 (SR form) Alzheimer's disease Research Unknown route South Korea Daewoong Pharmaceutical Originator South Korea Pharmaceutical Public

IMD3 (SR form) Gastric ulcer Research Unknown route South Korea Daewoong Pharmaceutical Owner South Korea Pharmaceutical Public

IMD4 (SR form) Thrombosis Research Unknown route South Korea

Alzheimer's disease Research Unknown route USA Bristol-Myers Squibb Originator USA Large Pharma, Biopharmaceutical Public

The J. David Gladstone Institutes Originator USA Institution N/A

BLV0703 Alzheimer's disease Research Unknown route Portugal BIOALVO Originator Portugal Biopharmaceutical Private

BLV200703 Neurodegenerative disorders Research Unknown route Portugal BIOALVO Owner Portugal Biopharmaceutical Private

SDGI-T200801 Parkinson's disease Research Unknown route Portugal

TAU Programme

Alzheimer's disease Research Parenteral France Rockefeller University Originator USA University N/A

Rockefeller University Owner USA University N/A

Sanofi Licensee World Large Pharma, Pharmaceutical Public

Virobay is developing VBY 129, a selective, orally

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-

daily dosing. Development is at the stage of early

research in the US.

Alzheimer's disease Research PO USA Unknown Originator USA Company

VBY 129 was originally being developed to treat

autoimmune disease. [CONT.]

Psoriasis Discontinued(I) PO USA Unknown Owner USA Company

Virobay Licensee USA Pharmaceutical Private

236

Research progranne: anti-beta-

amyloid antibodies - sanofi-

aventis/Rockefeller University

sanofi-aventis is developing a monoclonal

antibody, targeting specific forms of the amyloid

beta (Abeta) parenchymal plaque for the

treatment of Alzheimer's disease. sanofi-aventis

licensed a specific antibody from the Rockefeller

University to be studied. Preclinical research is

being conducted in France.


237

VBY 129 Cathepsin S inhibitors

235

Research programme: tau protein

modulators - BIOALVO

BIOALVO, located in Portugal, has a research

programme directed at tauopathies for the

treatment of neurodegenerative diseases such as

Alzheimer's disease and Frontotemporal

Dementia (FTD) with Parkinsonism. Tau protein

interacts with tubulin to stabilise microtubules

and promote tubulin assembly into microtubules.

Tau aggregation into neurofibrillary tangles (NFT)

is a major feature in some neurodegenerative

diseases [CONT.]

Tau protein modulators

233

Research programme: sustained-

release drugs - Daewoong

Pharmaceutical

Daewoong Pharmaceutical is developing

sustained-release incrementally modified drugs

(IMDs) for the treatment of thrombosis (IMD2),

Alzheimer's disease (IMD3), and gastric ulcers

(IMD4). The drugs are at the research stage of

development in South Korea.

Undefined mechanism

234

Research programme: Tau

dysfunction regulators - Bristol-

Myers Squib/Gladstone Institutes

Bristol-Myers Squib and the Gladstone Institutes

are conducting a discovery-based research

collaboration to identify and validate targets that

affect Tau dysfunction for the treatment of

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


Tau protein modulators

232

Research programme: subtype-

selective NMDA receptor modulators -

Mnemosyne Pharmaceuticals

Mnemosyne Pharmaceuticals is developing small

molecule therapeutics that target and modulate

the specific NMDA receptor subtypes of the

receptor subunit, NR2, as potential treatment for

cognitive and neuropsychiatric disorders.

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.]

Documents

Alzheimer's Disease (Preclinical & Research) · ALRT 4204 The Michael J. Fox Foundation for Parkinsons Research Collaborator USA Institution N/A ALRT-4204 ALRT4204 IRX-4204 IRX4204