QPS Global Capabilities Presentation

Find out how to achieve your nextdevelopment milestone ahead of timewww.qps.com

BioanalysisThat Way

Navigating Drug Development

ToxicologyThis Way

Early Stage ClinicalThis Way

Translational MedicineThat Way

Phase II – IV ClinicalThis Way

DMPKThat Way

NeuropharmacologyThis Way

Introduction

How do we introduce ourselves to you?

Corporate Mission, Vision of Success & ValuesHistoryBrief Company Overview Global PresenceQPS’ Linearly Integrated Core Competencies:

NeuropharmacologyDMPK ToxicologyBioanalytical Translational MedicineEarly Stage Clinical Development Phase II - IV Clinical Development

Why QPS?

April 18, 2023 Confidential 3

Corporate Mission, Vision of Success & Values

Mission

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.


Vision of Success



Values

Integrity – We make and keep promises and build trust through honesty, proactive communication, and reliability.Quality – We bring the highest level of technical expertise and judgment to our work.Customer Focus – We tap our global resources to provide service that is fast, flexible, and integrated.Commitment – We work hard to solve problems and deliver results. People – We treat people with dignity, respect, and fairness, and embrace our differences.Culture - We are friendly and fun. We provide opportunities to grow, we value loyalty and teamwork, and we recognize and reward performance.


History

Confidential 7April 18, 2023

Core Competencies:NeuropharmacologyDMPK (Discovery → Development)ToxicologyBioanalysis (Small Molecules → Biologics & Biosimilars) Translational Medicine (Genetic → Protein Biomarkers)Early Stage Clinical Development (Phase 0 → Phase IIa)Phase II - IV Clinical Development (Phase IIb → Phase IV)

Strategically located sites (1000+ employees) in North America, Europe & Asia

‘QPS offers breadth and depth, plus seamless

integrated service from drug discovery to regulatory

submission’

‘QPS is a global service provider to the pharmaceutical,

biotechnology and generic industries’

Brief Corporate Overview


‘Servicing customers all over the world’


QPS’ Linearly Integrated Core Competencies

Discovery/Candidate-Selection StageNeuropharmacology, ADME and Tolerability Studies to support Drug Discovery

Preclinical/Non-clinical Development StageAnimal Toxicology studies to support regulatory filingDevelopment DMPK studies to support regulatory filingRegulated Bioanalysis to support animal toxicology studiesImmunogenicity for PD and safety assessmentBiomarkers for animal pharmacology studiesPK/TK modeling

Clinical Development StagePhase I Healthy Volunteer studiesPhase II to IV Patient studiesDevelopment DMPK studies to support NDA filingRegulated Bioanalysis to support clinical studiesImmunogenicity for efficacy and safety monitoringPGx for patient stratification and efficacy monitoringBiomarkers for efficacy and safety monitoring Clinical PK/PD modeling

‘Have it all done in one place. Saves you time. Saves

you resources. Saves you money.’

Since it is a long way (…navigating your way….) to

the bedside’


Slide Deck Navigator

Navigate me directly to….

Global Neuropharmacology ServicesGlobal DMPK ServicesGlobal Toxicology ServicesGlobal Bioanalytical ServicesGlobal Translational Medicine ServicesGlobal Early Stage Clinical Development ServicesGlobal Phase II - IV Clinical Development ServicesWhy QPS?


‘helping you navigate your way through the screening and lead profiling

of your CNS drug candidates’

NEUROPHARMACOLOGY


Global Neuropharmacology Services

Brief Global Overview‘Neuropharmacology services on the basis of scientific excellence and international quality standards’

In Vitro Neuropharmacology ProfilingNeuronal Tissue CultureMode of ActionFull Safety Package

In Vivo Neuropharmacology ProfilingTransgenic and Non-transgenic Rats and MiceGeneration / Phenotyping of new Transgenic Rat and Mouse StrainsScreening for EfficacyLead ProfilingMolecular Biology, Biochemistry, Histology and BioanalyticsFull Safety Package



In Vitro Cell Culture‘In Vitro Cell Culture facilities equipped with the latest leading edge technologies’

Key Competences (non-exhaustive list)Isolation and Cultivation of Primary Rat/Mouse Neurons (Cortex, Hippocampus, TH-Neurons and Microglia)Isolation and Cultivation of Primary Chicken Cortical Neurons Cultivation of Cell Lines (SHSY-5Y, PC12, BV-2, HMO6, human fibroblasts and ARPE-19)Transfection (Over-expression, Knock Down) of Cell Lines (or Primary Cells)Functional Screening of Test Compounds in different Cell Culture Systems In VitroImmunofluorescence Analysis


Hutter-Paier Birgit

I am not sure which whats better...Neuro-Pharmacologyor Neuropharmacology


In Vitro Cell Culture‘Screening for efficacious lead drug candidates with a special focus on Neuroprotection’

Key Deliverables (non-exhaustive list)In vitro lesion models (MPP+, BSO, L-glutamate, Aβ1-42 a.s.o.) for AD, PD, Ischemia, AMDOxidative stress and mitochondrial activity Characterization of disease models in vitro (read outs: viability, apoptosis, necrosis and mitochondrial activity)Neurite outgrowth assay (primary hippocampal neurons, image based analysis)In vitro inflammation assays (cytokines, NO release)Screening for secretase and phosphorylation inhibitorsScreening for acetylcholine and butyrylcholine esteraseinhibitors



In Vivo Animal Models‘High quality and cost effective lead profiling’

Key Competences (non-exhaustive list)BreedingNon-transgenic Mice and Rat Models

MPTP (acute and chronic) induced Parkinson's disease MK-801-induced psychosisForced swim test (depression)Scopolamine induced learning or memory recall impairments 6-OHDA induced injury of dopaminergic neurons

Transgenic Mice and Rat ModelsAll relevant transgenic models for Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) research availableVarious genetically modified animal models: FTD, Amyotrophic Lateral Sclerosis, Niemann Pick Disease and Huntington’s DiseaseCross-breds of the different strains form complete models of human disease



In Vivo Animal Models‘Unique combination of in house characterized transgenic disease models with the most advanced pharmacological readouts’

Key Deliverables (non-exhaustive list)Acute and Chronic treatment via all common routes but also intrathecal injection and infusions, Alzet™ osmotic mini pumps with and without brain kit a.s.o.Behavioral Test Data (over 20 paradigms):

General Health and Motor Ability; Learning and Memory; Anxiety, Depression;Social Behavior, Attention and other Tests

Molecular Biology DataBiochemistry DataHistology Data



Molecular Biology‘Our validated protocols for molecular biological assays allow for quantitative evaluations which fulfill the strictest guidelines’

Genetic TestingGeneration of Expression Vectors for Transgenic AnimalsGeneration of Stably Transfected Cell-linesGeneration of Transgenic MiceGenotyping of Transgenic Animals by Quantitative PCRAnalysis of Gene Expression by RT-PCRQuantification of Virus Particles by PCRSafety Monitoring for Gene Therapy



Biochemistry‘Our GLP certified laboratory is ready to analyze all types of neurological biomarkers’

Bioanalysis in human blood or CSF samplesAmyloid beta, tau and phospho-tau, alpha SynucleinInflammation markerEnzyme activity: Cholinesterase, Monoaminooxidase and MyeloperoxidaseOxidative stressCholesterolAnalysis of disease related markers in brain, CSF, blood of Tg animal models; Assay Techniques:

ELISAWestern BlotMesoscale Discovery Multiplex AssaysEnzymatic assaysAmorfix Aggregated Aβ Assay A4(exclusively at QPS)



Histology‘World-class quantitative histopathology services backed by a highly dedicated team of histology, pathology, neurobiology and image analysis experts’

HistotechniquesAccording to principles of uniform, systematic random samplingVibratome, cryotome or slide microtomes

ImmunohistochemistryStandard stainings (e.g. H&E, Nissl, Congo Red, ThioS, Silver Stains)Antibody testing (specificity, sensitivity)Development of customer based multiple labelings (mainly fluorescent)> 400 primary and secondary antibodies on stock

Imaging on fully automatized microscopes High throughput multichannel mosaic imagingZ-stacking for high magnificationLarge data storage

QuantificationsAutomated and semi-automated measurementsTotal comprehensibility of obtained data to imagesCustomized quantification procedures and feasibility analyses


‘helping you navigate your way through the biotransformation of your drug’

DMPK


Global DMPK Services

Brief Global Overview‘DMPK services include the necessary studies for regulatory filing at the appropriate time and mechanistic studies when required’

PharmacokineticsSingle and Multiple Dose, Dose Proportionality, Absolute Bioavailability, PK/TK ModelingMass Balance/Excretion/Radiolabel StudiesFormulation Optimization, Intestinal Permeability, other Mechanistic Studies

Protein Binding; RBC/Plasma Distribution PartitioningProtein Covalent Binding

Tissue DistributionDiscovery QWBAQuantitative Whole-Body Autoradiography (QWBA)Micro-autoradiography (MARG)

MetabolismMetabolic Stability, Species ComparisonCYP450 Inhibition/InductionMetabolic Reaction Pathway ProfilingMetabolite Profiling & Identification – In Vitro, Preclinical, and Clinical

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Brief Global Overview‘QPS staff's experience is our biggest asset’

Team of senior DMPK scientists that all have on average 15+ years of pharmaceutical and biotech drug discovery and development experience.

All were DMPK representatives on discovery and/or development teams.Worked on > 50 INDs and > 10 NDAs.Worked in different therapeutic areas (Antiviral, CV, Oncology, etc.)The same group of scientists also has on average additional 10+ yrs of CRO experience.

Scientific Integrity and QualityEach DMPK management team member has in-depth skill sets in different fields:

Formulation & AbsorptionPharmacokinetics & Protein BindingQWBA & Micro-autoradiographyMetabolismMetabolite Identification

Program Development ConsultingAddress routine and mechanistic ADME issuesADME Summary for Regulatory Submission



Discovery ADME Studies‘QPS performs cost effective discovery ADME screens’

Metabolic stabilityCYP inhibition

“Validated” process with FDA approved specific probe substrates and chemical inhibitors

Protein bindingEquilibrium dialysis using conventional device or RED or HT96

Rodent PK – linearly integratedFormulationIn-life – Discrete or “N-in-1” dosingBioanalysis method development & sample analysis

“N-in-1” bioanalysis

PK calculationAverage turnaround time < 7.5 days from compound receipt to reporting of data



Candidate Selection Studies‘QPS experienced staff knows how to select your best IND candidates’

PharmacokineticsFormulation, dose proportionalityIntestinal permeabilityOther mechanistic studies for absorption and disposition (or clearance)

MetabolismSpecies comparison Metabolite profiling and/or identificationPilot CYP mapping

ExcretionRoute of elimination – BDC studies

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Radiolabeled Studies‘QPS has proven innovative study design and executional excellence for radiolabeled studies’

Combination Mass Balance /Excretion QWBA study to address MB, tissue distribution, and human radiation dosimetry questions

Better technical oversightEliminate the possibility of radiolabel degrading over an extended period of time between the two studies and the requirement of re-purificationIncrease efficiency using a single study protocol = ↓Study Cost

Metabolite Profiling and Identification in the same studyBoth ion trap and quadrupoles tandem mass spectrometers for different MSn experiments

Mass Balance Excretion Studies in Rats using 14C-labeled Cpds

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QPS Delaware DMPK Facility‘DMPK function with all necessary equipment and self-contained for speed’

Vivarium – focus on mouse and rat with nine (9) rodent rooms1 Surgical SuiteTriple cannulated animals for special models & in situ CSFIntracranial infusions for up to 7 days

Eight (8) bioanalytical labs for dose formulation, sample preparation, and analysisMass Balance Studies

Mass Balance Cages (Plastic and Glass)Micro-Filter Cages for Mice, Nude Mice and Rats

In Vitro cell culture LabS9, microsomes, and hepatocytesTumor cell-lines for xenografts

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Two (2) Autoradiography Labs for Macro- and Micro-autoradiographyLeica CM 3600 Cryomacrotome (whole-body)Leica Vibratome 9800 (whole-body)Leica CM 3050 S Cryomicrotome (individual organ/tissue)Molecular Dynamics Typhoon 9410 ImagerSix (6) Imaging Research MCID Elite Systems

Support Equipment: • Snap-freezing Equipment• Photography Equipment• Sample Oxidizers • Liquid Scintillation / Gamma Counters• Microplate Scintillation Counter• Radioactivity / LC Detectors




Dedicated LC/MS/MSThree (3) bioanalytical labs for sample preparation and analysisSix (6) Mass Spec (5 Sciex API 4000s, Finnigan LTQ ProteomeX)Waters UPLCs, Shimadzu VP-series LCs, Agilent 1100 LCs; LEAP HTC/PAL injectorsDetectors – UV/Vis, Fluorescence, ElectrochemicalTomtec Quadra 96 for 96-well sample preparation

Radio-QuantitationTwo (2) Packard Model 307 Sample OxidizersTwo (2) PE Tri-Carb 2800TR/2900TR Scintillation CountersPE TopCount® NXT Microplate Scintillation CounterPackard Cobra II Gamma CounterFour (4) Radioactivity DetectorsARC XFlow System; Off-line Fraction Collectors



QPS Delaware DMPK Facility‘DMPK function with all necessary accreditation, certifications, permits, and licenses’

AAALAC AccreditationABC LicenseCDC Permit DEA Permit for Scheduled Control Substances (I-V)Federal Fish & Wildlife PermitNRC License for Radiochemicals

3H, 14C, 32P, 33P, 35S, 45Ca, 51Cr, 90Y, 99mTc, 111In, 125I, 188ReOLAW AssuranceORCA CertificationUSDA Permit


‘helping you navigate your way through the safety of your drug’

Toxicology


Global Toxicology Services

Brief Global Overview‘QPS CTPS Taiwan is one of the most experienced toxicology centers in Asia’

Track RecordOver 1000 GLP Studies conducted since 1997 17 dossiers compiled for US FDA IND submission18 dossiers compiled for Taiwan IND submission

Accreditations & Compliance:AAALAC Accreditation since 2000Taiwan Accreditation Foundation (TAF) ISO 17025Taiwan Department of Health (DOH) GLPOECD (TAF) GLPUS FDA GLP compliance



Safety Evaluations‘QPS CTPS is able to provide you the complete battery of toxicological tests that is needed for the filing of your IND submission’

General & Reproductive ToxicologyGenetic Toxicology General (non-GLP) Toxicity TestingPharmacokinetics with BioanalysisBiocompatibility TestingTopical Toxicity Testing



General & Reproductive Toxicology‘QPS CTPS is able to provide you with a comprehensive package of in vivo toxicology studies’

Single Dose Toxicity StudiesRepeat Dose Toxicity Studies

Up to 6 months in durationRoutes of administration: oral, intravenous (injection and infusion), intramuscular, subcutaneous, intraperitoneal and othersAnimal species: mice, rats, guinea pigs, hamsters, rabbits, dogs ……….and cynomolgus monkeys coming soon!

Reproductive ToxicologyFertilityTeratologyAnimal species: rat and rabbit

Clinical PathologyUrine AnalysisHematologySerum Chemistry

HistopathologyTissue and Slide PreparationTissue ImageQA of Scanned Slides, Pathology Consultation and Evaluation by US Board-Certified Pathologist



Genetic Toxicology‘QPS CTPS is able to provide you a broad panel of in-house conducted genotoxicity tests’

Gene Mutation AssaysAmes Test/Mini-Ames TestHPRT gene mutation assayIn Vitro mouse lymphoma assay

Cytogenetic AssaysSister chromatid exchange assayChromosome aberration assay

Micronucleus AssaysMicronucleus assay in CHO cells and

human peripheral lymphocytesMouse micronucleus assay

Cell Transformation AssayIn Vitro cell transformation assay



Biocompatibility Testing‘QPS CTPS is able to provide you with this high-quality niche service which primarily involves the toxicity testing of medical devices’

Acute Systemic Toxicity TestPyrogen and LAL Test

Animal species: rabbitIntracutaneous Irritation TestSkin Sensitization TestCytotoxicity TestIn Vitro HemolysisMutagenicity TestImplantation Test



Topical Toxicity Testing‘QPS CTPS is able to provide you with other high-quality niche services which primarily involves the toxicity testing of dermatological and cosmetic products’

Irritation StudiesEye irritation testDermal irritation testAnimal species: rabbit

Skin Sensitization TestingBuehler testMaximization testAnimal species: guinea pig



Why QPS for Toxicology‘QPS CTPS Taiwan supports you with a quality operation for the highest value ’

US owned, 15-year US GLP study history (1997 - present)Highly experienced toxicologists, US, EU and Japan trained (DABT, DJST)Highly experienced QA, registered with SQALarge/small molecule, device development expertiseOn-site clinical pathology, histopathology by DACVP, dose analysis, bioanalyticalEstablished global procedures for sample shipping and data analysisRemote video study monitoring Gold standard animal sourcing (Charles River; Marshall Beijing)State of the art automatic data collection system (Xybion Pristima®)Considerable price savings versus US site labs


‘helping you navigate your way through the measurement of your drug’

Bioanalytical


Global Bioanalytical Services

Brief Global Overview‘QPS is a global leader in bioanalysis for both small and large molecules’

Small molecules – using mass spectrometric techniquesLarge Molecules - using ligand binding assay techniquesGlobal coverage of bioanalytical services with local presence in North America, Europe, India and AsiaWorld leading…

Specialists (> 150 technical staff)State-of-the-art equipment (API5500Q, API 5000, UPLC-MS/MS, ICP-MS, MSD6000 and Gyros™)Capacity (> 45 Mass Specs)Capabilities: LC-MS/MS, ICP-MS, LC-UV, LC-Flu, LC-ECD, LC-RFD, LBA, Hybridization-ELISA and RIA

Extensive validated assay list (> 800 assays and growing)Rapid assay development, validation, sample analysisSupporting a full range of development from Preclinical to Late Stage Clinical programsImmunogenicity & Neutralizing Antibody Activity AssessmentCentral Lab Services: Sample Logistics / Sample Repository / Preparation and Distribution of Sampling Kits



Small Molecule LC-MS/MS‘QPS is a global leader in bioanalysis

for small molecules and is able to analyze samples coming from

different types of studies, containing a wide variety of compound

structures and biological matrices’

Bioanalytical Method Development & Validation Sample Analysis for different evaluation purposes:

Pharmacokinetic (PK) screeningToxicokinetic (TK) studiesClinical PK/Bioavailability studiesBioequivalency studiesTherapeutic drug monitoring studiesBiomarker studiesDrug-drug interaction studies

Sample Analysis of different compound structures:

Oligonucleotides AnalysisPeptide Analysis

Sample Analysis in different biological matrices:

Dried Blood SpotsTissues



Large Molecule ImmunoBioanalysis

‘QPS is a global leader in bioanalysis for large molecules and is able to analyze

samples coming from different types of studies, containing a wide variety of compound structures and biological

matrices’

Bioanalytical Method Development & Validation for Biologics and BiosimilarsSample Analysis for different evaluation purposes:

Pharmacokinetic (PK) screening Toxicokinetic (TK) studiesPK/Bioavailability studiesBioequivalency studiesTherapeutic drug monitoring studiesBiomarker studiesDrug-drug interaction studies

Immunogenicity monitoring using four-tier approach:

ScreeningConfirmatory (immunodepletion) Titer assessment (quantification)Cell-based neutralizing antibody detection



‘QPS is an experienced provider of GLP trace and ultra-trace elemental analysis in preclinical and clinical studies by (LC)-ICP-MS. Applications range from quantitative, high throughput analysis (700 samples/day) to qualitative, stability or metabolite profiling studies .

Sample matrices are blood, plasma, urine, feces, tissue or formulation. Examples of routine applications at QPS using ICP-MS in drug development studies are:

Total and free Platinum (Pt) in oncology studies

Platinum (Pt) in plasma and urine by LC-ICP-MS for the metabolite profiling of a new platinum compounds

Gadolinium (Gd) in plasma and urine by ICP-MS supporting clinical studies with MRI contrast agents and formulations

Magnesium (Mg), Calcium (Ca), and Phosphate (P) in food and feces for supporting a mass balance study of a new phosphate binder

Ag, Zn, Al, Pd, Gd, Tc, I, P, S, Mn, Co. Ni, Se, Cu, As, Si and Eu in different biological or pharmaceutical matrices

Fe in Transferrin Co in Vitamin B12

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Elemental Analysis in Drug Development


Large Molecule LC-MS/MS‘QPS believes strongly in this novel

bioanalytical application of LC-MS/MS and can show you some

stunning results’

Bioanalytical Method Development and Validation, and Sample Analysis

OligonucleotidesPeptidesProteinsMonoclonal Antibodies



QPS Delaware GLP Facility – Newark, Delaware, USA‘QPS Delaware is a well-established high quality, cost-effective sourcing solution for the analysis of PK and PD samples coming from preclinical and clinical studies conducted in the USA’

Small Molecule LC/MS/MS29 (25 Sciex API 4000 and 4 Sciex API 5000)

Large Molecule ImmunoBioanalysisCapability in PK, Immunogenicity, NAb assay, and biomarkersVarious technology platforms: ELISA, MSD ECL, GYROS and RIA

Hundreds of validated methods (DDI CoMeds) availableComplete list available on website (www.qps.com)WATSON LIMS System v7.4.1 with Immune Response Module(IRM)

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QPS Netherlands GLP Facility – Groningen, the Netherlands‘QPS Netherlands is a well established high quality, cost-effective sourcing solution for the analysis of PK and PD samples coming from preclinical and clinical studies conducted in Europe’

Small Molecule LC/MS/MS8 Triple Quadrupoles Mass Spec (API 5500Q, 4000, 3000)

Large Molecule ImmunoBioanalysisCapability in PK, Immunogenicity, NAb assay, and Biomarkers

Elemental Spectrometry (ICP-MS)ICP-MS; total analysis, product testing, free and protein bound, e.g., Pt for oncology LC-ICP-MS; speciation, metabolite identification, stability/degradation studiesUV-Vis Spectrometry, determination of radioactive labeled compounds

Hundreds of validated assay methods (DDI CoMeds) availableComplete list available on website (www.qps.com)Logistically closely linked to the phase I unit to enable fast turnaround of plasma concentration data of laboratory biomarkers and drug candidates during the conduct of first-in man programs (SAD, MAD), human mass balance and microdosing studies, and trials with instable compounds

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QPS Bioserve GLP Facility – Hyderabad, India‘QPS-Bioserve is a high quality, cost-effective sourcing solution for the analysis of PK samples coming from bioequivalence studies conducted by QPS-Bioserve’s own phase I Unit and from clinical studies performed in India’

Small Molecule LC/MS/MS7 Triple Quadrupoles Mass Spec (2 Sciex API 3200 and 5 Sciex API 4000)

Hundreds of generic methods availableComplete list available on website www.qps.comQPS-Bioserve has a dedicated and experienced Pharmacokinetics & Statistics team, with expertise in the application and presentation of PK and statistical principles, critical for successful approval of generic product submissions:

Study design, sample size and statistical power estimationBioequivalence analysisPK and PK/ PD analysisIn Vitro - In Vivo Correlation (with Pharsight™ IVIVC toolkit software)WinNonlin™ for PK analysis and SAS for statistical analysisFinal Report submissions in E3/ CTD format


http://www.qps.com/


QPS Taiwan GLP Facility – Taipei, Taiwan‘QPS-Taiwan is a high quality, cost-effective sourcing solution for the analysis of PK samples coming from bioequivalence studies conducted by QPS-Bioserve’s own Phase I Unit and from clinical studies performed in Asia’

Small Molecule LC/MS/MS4 Triple Quadrupoles Mass Spec (4 Sciex API 4000)

Large Molecule ImmunoBioanalysisCapability in PK, Immunogenicity, Nab Assay, and Biomarkers

Hundreds of generic methods availableComplete list available on website (www.qps.com)WATSON LIMS System v 6.4 (WATSON v7.4.1 Coming Soon!)


http://www.qps.com/

‘helping you navigate your way through the efficacy of your drug’

Translational Medicine


Global TLM Services

Brief Global Overview‘As an experienced provider of translational medicine services, QPS offers solutions to help guide drug development teams at various stages, including patient stratification, toxicity prediction, evaluation of PK profiles, dose determination, and treatment decisions’

BiomarkersPD protein or biochemical markersVarious biomarker assay platforms (ELISA, Immulite®, Bioplex®, MSD® Imager 6000 ECL, GYROS, Flow Cytometry, LC-MS/MS and LC-ECD) Cell-based & functional assaysWestern Blot analysis & quantificationRadioligand binding assayOn-site cell stimulation and cytokine biomarker panel evaluation

Pharmacogenomics (PGx)DNA & RNA isolation and banking Genotyping (SNPs, insertions, deletions, copy numbers, etc.)CpG methylation quantificationRNA isolation & expression profiling (qRT-PCR)


Global TLM Services

Biomarker Panels‘QPS offers laboratory biomarker panels for many different therapeutic areas’

Adrenal/Pituitary Disorders Diabetes/Lipid Metabolism/ Carbohydrate Metabolism

Reproductive Endocrinology

Allergy Gastrointestinal Thyroid Function

Alzheimer’s Disease Hemostasis/Angiogenesis

Anemia Infectious Disease

Autoimmune Disease Inflammation/Immune Status/Cell Response

Bone Disease / Metabolism Oncology (Tumor/Neoplasia Markers)

Cardiac Markers Phenotypic Markers of Drug Metabolism

Cell Response Renal Toxicity and Function


Global TLM Services

Pharmacogenomics (PGx)‘Genotyping and gene expression analysis services are offered by QPS to help ‘individualize’ disease therapies’

Nucleic Acids Isolation (DNA & RNA) and BankingGenotyping (SNPs, Insertions, Deletions, Copy numbers, etc.) CYP450 Genotyping Assays (CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6 genotyping panels)Genotyping Assays for Other Drug Metabolizing Enzymes (NAT1, NAT2, UGT1A1, CDA)Genotying Assays for Transporters (ABCG2, SLCO1B1)Genotyping Assays for Oncology (BRAF, KRAS, PIK3CA) Genotyping Assays for Alzheimer’s Disease (ApoE, PPP3R1)Genotyping Assays for Warfarin Therapy (CYP2C9*2, CYP2C9*3, and VKORC1 (-1639 G>A))CpG Methylation QuantGene Expression Profiling in various matrices (qRT-PCR)

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Immunogenicity/Anti-Drug Antibody Testing‘QPS is an expert in immunogenicity/ADA & Nab testing and has all the necessary knowledge and assays technologies at its disposal’

QPS has supported 50+ biologic drug development programs for 23 sponsors (24 proteins and 26 therapeutic antibodies) for which over 120 studies were performed.Anti-Drug-Antibodies (Screening, Confirmation, and Titering) by ELISA or MSD ECLAntibody Generation Critical Reagent LabelingCell Based Neutralizing Antibody (NAb) Assays Cell Banking and MaintenanceTechnology Transfer Custom Method Development and Optimization

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Global TLM Services

Neutralizing Antibody Assays‘QPS is an expert in NAb testing and is able to apply its extensive knowledge and application of new assay technologies to your benefit’

Since 2002 > 50 Studies conducted for 7 Sponsors ELISACell-Based Functional Assays, e.g. cell viability assayOther Functional Assays, e.g. activity assay Receptor Binding Assays


Global TLM Services

Novel Biomarker Assay Development‘QPS is a frontrunner in adopting new assay technologies for biomarkers’

Various Technology Platforms (ELISA, BioPlex™, Immulite™, MSD ECL, Gyrolab™ and BD FACS Canto II)Cell-Based AssaysPharmacodynamic (PD) & Safety MarkersMultiplexing Genetic Markers (CYP450 TaqMan or Affymetrix DMET genechips)Pharmacodynamic (PD) Assays On-Site Cell Stimulation and Biomarker AnalysisFit-For-Purpose Biomarker Assay Development and Validation (various matrices)Protocol Design

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Global TLM Services

Analytical Platforms‘QPS scientists and laboratory technicians are used to work and have many validated assays on many different assay technology platforms’

ELISA Pyrosequencing Technology Platform

Roche Modular P® Affymetrix GeneChip Microarray System

Siemens Immulite® TaqMan Real-Time PCR System

Bioplex® (Luminex™) Gradient Gel Electrophoresis (GGE)

Meso Scale Discovery (MSD®) ECL Platform (SECTOR™ PR100 and Imager 6000)

HPLC/UHPLC/UV/Fluorescence/ECD

Gyrolab™ LC – MS/MSBD FACS Canto II® Ultracentrifugation

RIA Western Blot Analysis

Radioligand Binding Assay (SPA)


‘helping you navigate your way through the complex challenges of the early

development of your drug’

Global Early Stage Clinical Research



Brief Global Overview‘QPS is a global leader in Phase I/IIa studies’

QPS has one of the world’s largest Phase 1 site offerings with almost 500 Phase I beds on three continents:

QPS offers a complete spectrum of early phase study types:


240 in Springfield, Missouri, USA 75 in South Miami, Florida, USA 20 in Hollywood, Florida, USA 92 in Hyderabad, India40 in Taipei, Taiwan 58 in Groningen, The Netherlands

First-in-Man Programs (SAD + MAD + FE + CYP450) Human Mass Balance studies Microdosing studies Imaging (PET, fMRI) studiesClinical PK/PD studies Drug-Drug Interaction studiesCardiac Safety/Thorough QT/QTc studies Bioavailability/Bioequivalence/ANDA studiesVaccine studies Specialty PopulationsProof-of-Concept (PoC) in multiple therapeutic areas


Biomarker Support‘QPS is not only capable of conducting phase 1 studies for you in specialty and patient populations but QPS is also capable of doing the additional measurement and interpretation of therapeutic-specific biomarker data as well’Adrenal / Pituitary Disorders Diabetes / Lipid

Metabolism / Carbohydrate Metabolism

Reproductive Endocrinology

Allergy / Asthma / COPD Gastrointestinal Thyroid FunctionAlzheimer’s Disease Hemostasis / Angiogenesis

Anemia Infectious Disease

Autoimmune Disease Inflammation / Immune Status / Cell Response

Bone Disease / Metabolism Oncology (Tumor / Neoplasia Markers)

Cardiac Markers Phenotypic Markers of Drug Metabolism

Cell Response Renal Toxicity and Function



Full-Service Early Stage CRO ‘QPS is a full service early stage CRO that is not only capable of providing the clinical conduct of your Phase 1 study but has the ability to provide the front and back end services as well’

Review of Preclinical DataDesign and Preparation of the TrialClinical Project ManagementPreparation of the Study Protocol, Informed Consent, and Case Report FormsClinical ConductClinical Data ManagementBiostatisticsBioanalysis/Biomarker AssaysConduct PK/PD and/or Pop PK/PD DataAnalysis and ModelingPrepare PK/PD ReportPrepare and Publish Fully IntegratedClinical Study ReportsMonitoringPharmacovigilance



QPS Bio-Kinetic – Springfield, Missouri, USA‘QPS Bio-Kinetic is ideally suited to conduct a wide variety of phase I studies, especially when substantial numbers of volunteers need to be recruited in record breaking time’

5 Clinical Units with 240 beds on one CampusOver 1000 studies completed since 199417 FDA InspectionsClinical Staff Experience

8+ years average length of employmentLess than 3% staff turnover rate

37,000 subjects in database Specialty Studies

VaccinePostmenopausalGeriatricBirth Control and Birth Control NaïveCardiac Safety/TQTc



QPS MRA – South Miami, Florida, USA‘QPS MRA conducts complex phase I studies that other sites are unable to execute’

16,000 Square Feet facility50 actively monitored bedsUnique high-level medical oversightHealthy volunteers (FIM, SAD, MAD), specialty populations, and Proof-of-Concept (PoC) in multiple therapeutic areasConsistent high enroller, often exceeding contracted subject allocationExcellent subject retention (over 90%)


Specialty & PoC PopulationsElderly ObesityHepatic Insufficiency Parkinson’sRenal Insufficiency DepressionPsoriasis Pediatric ADHDType II Diabetes Arthritis

RheumatoidOsteoarthritis

Post-Menopausal LupusHypertension On Demand


QPS Broward – Hollywood, Florida, USA‘QPS Broward is an experienced Phase I site with a great track record in reliable and efficient study conduct’

BRG established in 2000 – 10,000 sq. ft. facilityDavid Seiden, MD – Board-Certified in Sleep, Neurology, and PsychiatryHealthy Volunteers/Special Populations – Sleep, Vaccines, Depression, Anxiety, ADHD, Birth Control, T2DM, Obesity, Parkinson's, Alzheimer's, OA etc…Over 150 Clinical Trials completed – Phase I-IVBRG Facility

20 beds 15 ACRP-Certified Coordinators, Nurse Practitioner, Neuropsychologist, RN’s, LPN’s, Sleep TechniciansQA / Regulatory deptsLaboratory, EEG, ECG, pulse oximetry recording equipment, polysomnography, refrigerators, centrifuge, freezers (-20 C and -70 C)



QPS Bioserve – Hyderabad, India‘QPS Bioserve is a full service Phase I site with a long list of regulatory approvals for generic products that have been tested at this site’

Full-service CRO, all aspects of study (from study design to final report generation) are conducted in-houseISO 9001:2008 certified organizationApproved by the Drugs Controller General of India (DCGI)Audited by the US-FDA in March 2008 & July 2009 (no 483s)Inspected by UK MHRA and WHO in 2010Over 630 conventional BA/BE studies conducted for variousregulatory agencies (130 are pivotal studies)Twenty (20) products successfully approved by US FDAClinical End Point Studies: QPS Bioserve has experience in using PD end points or other acceptable surrogate parameters to establish bioequivalence for products (e.g. locally acting/topical preparations) for which it is impossible to use PK endpoints.Examples: Sucralfate (suspension), Pentosan Polysulfate (capsules), Adapalene (gel)Pharmacoscintigraphic ImagingNCE PK studies like Food Effect, Dose Proportionality and Drug-Drug Interaction



QPS Taiwan – Taipei, Taiwan‘QPS Taiwan is a full service Phase I site with a long list of regulatory approvals for locally manufactured generic products’.

Full-service CRO, all aspects of study (from study design to final report generation) are conducted in-houseBioavailability / Bioequivalence StudiesHealthy Normal PopulationsPK in Cancer Patient PopulationsScaled Average BioequivalenceConventional BA/BE studies conducted for various regulatory agenciesMore than 40 products successfully approved by Taiwan FDA



QPS Netherlands – Groningen, the Netherlands‘QPS Netherlands is ideally suited to conduct your FIM and more complex phase I programs’

Hospital-based Phase I unit Over 100 studies completed: 20 first-in-man programs (of which 12 with biologics); 7 PET studies; 6 Oral Contraceptive (OC) interaction studiesFast and easy access to top-notch medical, clinical-pharmacological, medical and scientific expertiseParallel submission to Competent Authority (CCMO) and local Ethics Committee (EC) resulting in Clinical Trial Approval within 14 days. Substantial amendments: 48h turnaround time; Dose escalations: 24h turnaround timeLogistically closely linked to the bioanalytical laboratory to enable fast turnaround of plasma concentration data of laboratory biomarkers and drug candidatesSpecialty Studies:


Multi-Purpose Umbrella Protocols (SAD + MAD + food effect + CYP450 phenotyping) - adaptive designs with flexible dosing escalation schemes

Female Health Care (OC Interaction, Lactation and Fertility studies)Validated neuropathic (capsaicin) and acute (M3 extraction)pain models

Pulmonary/Respiratory MedicineImaging (PET, fMRI) studiesContinuous) CSF sampling in Healthy Volunteers and (Alzheimer) Patients(Radiolabel (14C) Human Microdosing and Mass Balance studies

‘helping you navigate your drug all the way across the finish line’

Global Phase II-IV Clinical Research



Brief Global Overview‘Widely recognized for achieving high-quality study data and high patient enrollment rates, QPS’ site management & monitoring teams bring you years of experience’

Phase I - IV Project and Study ManagementClinical Trial MonitoringClinical Trial Logistics and SuppliesData ManagementBiostatisticsMedical Writing



Phase II – IV Clinical Study Experience


Phase II67 Studies

Phase III59 Studies

Phase IV63 Studies

N = 189 Studies


Top 10 Therapeutic Indications



‘Apart from stand-alone clinical research activities, QPS is also able to manage your entire clinical drug development program’

Clinical Consultancy and support throughProject Life CycleDesign of Clinical Program and Individual StudiesQPS will conduct your project according to the protocol with high quality data withintimelines and within budget

Project Management



Site Management & Monitoring‘Let QPS manage your Clinical Research Activities’


Site Selection, Patient Recruitment and Site Logistics

Site TrainingStudy Reference ManualProtocol/Study MaterialsOne-on-One SessionsTrain-the-Trainer SessionsOnline PresentationsOnline Tutorials for EDC

EDC On-Site MonitoringStudy InitiationInterim VisitsStudy Close Out

Regulatory Document Collection, Review and Submission

Site Audit and/or QualificationPer RequestFor Cause


‘State-of-the-art clinical trial management and electronic data capture systems enable QPS to deliver first rate data management services’

Streamlined clinical information capabilities between QPS and Investigational Sites/BranchesClinical Database

Paper based CRFeCRF

Fast Data Base Lock

Data Management



Data Analysis for Late Stage Clinical StudiesSAS ProgrammingExports of Tables, Figures and Listings (TFLs)PK / PD Analysis (including Pop PK)

Pharmacokinetic and statistical consultancyStudy design including optimization of PK sampling and power evaluation of population size enrolledNon-compartmental and compartmental PK modelingPopulation pharmacokineticsStand-alone PK/PD report

‘State-of-the-art clinical trial management and electronic data capture

systems enable QPS to deliver first rate biostatistics services’

Biostatistics


‘QPS can take care of all your medical writing needs’Clinical Study ProtocolInvestigator’s BrochureIMPD (Investigational Medicinal Product Dossier)ICFScientific PublicationsFinal Clinical Report (CTD or eCTD)


Medical Writing



Clinical Advantages

Global capabilities yielding significant cost savingsLow turn-over of QPS staff, specifically CRAsAccess to a large network of investigatorsExperienced central management and local expertisePersonal touch of a boutique CRO but with global capabilities


Why QPS?

What sets us apart?‘QPS will help you navigate your way through the complex challenges of the development of your drug….and while navigating your way, you will enjoy having….’

Direct access to QPS’ people's minds!Direct access to key personnelDirect access to vast amounts of drug discovery & development experienceScientific expertise spanning preclinicalwork to drug approval

Direct access to QPS’ people's hearts!EnthusiasmProfessional attitudeFlexibility in meeting client needsFocus on long-term professional customer relationships

Direct access to QPS’ people's hands!Responsive and committed to your timelines Cost effective approach for program development


QPS Global Capabilities Presentation

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Transcript of QPS Global Capabilities Presentation