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NEUROPHARMACOLOGY

Alzheimer - Parkinson - Hun�ngton - ALS - Psychiatric Disorders

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QPS AUSTRIA THE COMPANY

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Our profound expertise in neuroscience and more than a decade of experience in contract research results in a sustainable advantage for our customers.

We offer you a sophisticated range of validated transgenic and non-transgenic in vivo and in vitro models in order to make sure

that your new chemical or biological entities get profiled in depth using both novel and established drug targets that may play a role in the complex etiology of neuro-degenerative disease

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QPS AUSTRIA MISSION STATEMENT

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We are committed to combine scientific experience, state of the art techniques and excellent communication to deliver superior support in drug development.

Our mission is to accelerate the development of medicines worldwide by enabling cost effective breakthroughs in pharmaceutical innovation.

QPS is a global leader in contract research.We are known for our quality, technical expertise, efficiency and customer focus.

Our passionate and productive work creates value for patients and customers while creating opportunities for employees to grow and thrive.

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EXPERIENCED PARTNER IN DRUG DEVELOPMENTT

QPS Austria has developed multiple methods for testing and evaluating new potential treatment approaches for neurological and psychiatric indications.

The close link to state of the art science enables us to reliably assess the potential of new compounds.

The wide range of assays and evaluation methods allows our customers to gain the most comprehensive information about their drug candidates.

Outstanding quality and reliable timelines are our dedication. QPS Austria can help to significantly reduce the time to approval.

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CELL BASED DRUG TESTING

QPS Austria provides a comprehensive portfolio of standardized cell culture systems, including primary neurons fromrat, mouse and chicken as well as transgenic & non transgenic cell

Cultures can be analysed for a wide spectrum of parameters:

Cell viability, apoptosis, necrosis Mitochondrial impairment Inflammation related parameters Neurite growth Disease related markers Secretase inhibition or modulation Tau phosphorylation Broad range of analytes on a

multiplex platform

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We continuously establish new models and perform validations on request.

lines.

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DISEASE RELATED IN VITRODRUG TESTING OPTIONS

At QPS Austria the effects of your compounds on the most well-known hallmarks of neurodegenerative diseases can be tested in validated assays.

Amyloid pathology can be investigated using several different aggregation, toxicity and secretase assays. Drug mediated alteration of Tau phosphorylation can be studied using cells overexpressing human mutant Tau441 or primary cultured neurons.

Parkinson drug development projects can be supported by performing studies with dopaminergic neuroblastoma cells, MPP+ lesions and other disease specific models.

Inflammation represents a major topic in several neurodegenera-tive diseases. Consequently QPS established a range of assays to study cytokines, NO release and others.

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BIOANALYTICALSERVICES

QPS Austria is a GLP certified CRO and experienced in high quality performance of various bioanalytical tasks within mono- or multicentral clinical studies and other projects.

Covering the entire drug development process, biomarker and numerous other analyses are performed by an experienced team.

Synucleins Cellular aggregates (TDP-43, SOD1) Neurotransmitters

Beyond the established assays weprovide customized development

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Tau & pTau species Amyloid peptides (all Aβ species & aggregation states) Inflammation markers

and validation assays.

Lipid profile

Neurotrophic factors

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GENERATION ANDCHARACTERIZATIONOF TRANSGENIC ANIMALS

New drug targets opening effective pathways to treat neuro-degenerative diseases represent an interesting challenge and new opportunities in drug development. QPS Austria is experienced in creating and validating new transgenic animals. Custom tailored transgenic mouse and rat models are perfect tools to perform proof of concept studies.

Beyond the generation of the desired animal model we routinely

run breeding programs using any rat or mouse model available. As a further option we can apply viral vectors carrying the genetic information to be expressed.

The genetic, behavioral, histological and biochemical characterisation and validation of the newly created models is performed by our experienced team at QPS Austria.

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QPS Austria provides a wide range of transgenic mouse and rat models. The most requested models are the following:

Alzheimer’s disease APPSL

APP x hQCSL

5 x FAD

TAU441

tg2576

Parkinson’s disease human wt alpha-synuclein D-line human wt alpha-synuclein Line 61 human alpha-synuclein A53T Huntington’s disease R6/2 mouse

Others SOD1-G93A mouse (ALS) TDP43-TARDBP (ALS & FTD)

TRANSGENICMOUSE AND RAT MODELS

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NPC1 -/- (Niemann Pick Disease)

APP x ApoB100SL

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Test compounds are applied via validated routes like ip, iv, in, po, im, sc but also intrathecally, intraventri-cularly or with devices like osmotic mini pumps or implantable pellets.Drug application via drinking water or diet is also always an option.

Moreover, we apply viruses (e.g. LV or AAV) for gene therapeutic or other approaches.

Skilled personnel is able to sample

blood as well as cerebrospinal fluid in vivo.

At the end of a drug application period any organ as well as blood and cerebrospinal fluid can be sampled in sufficient amounts and processed further for histological and / or biochemical investigations made in house or at any facility defined by the sponsor.

SUPERIOR DRUG APPLICATION & SAMPLING

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In many of the transgenic and non-transgenic disease models drug mediated behavioral changes belong to the most important experimental outcomes.

All behavioral paradigms are perfor-med, recorded and evaluated using automated up to date equipment.

Beyond experimental paradigms as listed below we perform high level techniques for drug testing and phenotyping including homecage phenotyping and others.

Poke hole activity Rota rod Two choice swim test New object recognition Social interaction Prepulse inhibition Ultrasound vocalisation

DRUG TESTING SERVICESBEHAVIOR

Active and passive avoidance Beam walk Challenging beam walk Pole test Y – maze T – maze Elevated plus maze Contextual fear conditioning Fear conditioning Cylinder test Forced swim test Morris water maze Buried food test Open field

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Studies at QPS Austria GmbH provide quantitative and qualitative histological readouts. In the scope of neurodegenerative diseases pathological hallmark detection is highly standardized like:

Plaque quantification (e.g. 6E10, ThioflavinS, Congo red) Inflammation markers (e.g Mac-1, Iba-1, GFAP)

α-synuclein: quantification of Lewy body counts (e.g. α-syn, phospho-α-syn, Campbell Switzer) Neuron and synaptic counts (e.g. TH, NeuN, Synaptophysin) Tau pathology (e.g. AT180, HT7, AT270) Microbleeding and BBB permeability (e.g. Prussian blue, HRP) Ischemic damage (e.g. TTC and NBT staining)

Beyond standard evaluations our team will be happy to help with expertise in development of appropriate study setups and protocols. As special services we are able to offer unbiased stereology and electron micro - scopy beside standard brightfield and fluorescence microscopy.

DRUG TESTING SERVICESHISTOLOGICAL EVALUATION

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QPS' reputation in neuro-pharmacology and the acknowledged bioanalytical experience in all phases of drug discovery and development create a unique combination of services to study pharmacokinetics, and pharmacodynamics of discovery candidates developed specifically for neurological indications.

These services combine: Administration of candidates in

various tissues (incl. intrathecal) Usage of transgenic animals

Behavioral studies Various sampling techniques (including brain, CSF, spinal cord)

Wide range of bioanalytical methods for PK and biomarker assessments.

RAPID IN VIVO PK/PD/EFFICACY SCREENINGIN TG & NTG ANIMALS

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Our regional facilities and ofces are located in:

USA, China, Japan, Taiwan, India, Netherlands, Austria, Czech Republic, Croatia, Israel, Serbia, Bosnia, Hungary, Spain, Germany,

United Kingdom, Slovakia, Bulgaria, Romania, Lithuania, Ukraine, Poland, France and South Korea

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27QPS helps you navigate

QPS is a reputable and profitableprovider of world-class pharma- ceutical development services,possessing unparalleled scientificexpertise within our core competencies:

Neuropharmacology DMPK Toxicology Bioanalysis Translational Medicine Early Stage Clinical Phase II - IV Clinical Program Management

QPS WORLDWIDEOUR CORE COMPETENCIES

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QPS AUSTRIA GMBH Parkring 12 | 8074 Grambach | Austria | Tel.: +43 316 258111ofce-austria@qps.com | www.qps-austria.com | www.qps.com