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QPS Global Capabilities Presentation

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QPS is a GCP/GLP-compliant CRO that supports discovery, preclinical, and clinical drug development. We provide quality services in DMPK, Toxicology, Translational Medicine Research, Early Stage and Phase II - IV Clinical Research to clients worldwide. Our regional laboratories are located at our headquarters in Newark, DE, USA; Springfield, MO, USA; Groningen, The Netherlands; Hyderabad, India; and Taipei, Taiwan.

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QPS Global Capabilities Presentation

  1. 1. Find out how to achieve your next development milestone ahead of time www.qps.com
  2. 2. Bioanalysis That Way Navigating Drug Development Toxicology This Way Early Stage Clinical This Way Translational Medicine That Way Phase II – IV Clinical This Way DMPK That Way Neuropharmacology This Way
  3. 3. Introduction How do we introduce ourselves to you? Corporate Mission, Vision of Success & Values History Brief Company Overview Global Presence QPS’ Linearly Integrated Core Competencies: Neuropharmacology DMPK Toxicology Bioanalytical Translational Medicine Early Stage Clinical Development Phase II - IV Clinical Development Why QPS? 29 August 2013 Confidential 3
  4. 4. Corporate Mission, Vision of Success & Values Mission To accelerate the development of medicines worldwide by enabling cost effective breakthroughs in pharmaceutical innovation 29 August 2013 Confidential 4
  5. 5. 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. Corporate Mission, Vision of Success & Values Vision of Success 29 August 2013 Confidential 5
  6. 6. Corporate Mission, Vision of Success & Values 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. 29 August 2013 Confidential 6
  7. 7. History Confidential 729 August 2013
  8. 8. Core Competencies: Neuropharmacology DMPK (Discovery → Development) Toxicology Bioanalysis (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, biotechnolo gy and generic industries’ Brief Corporate Overview 29 August 2013 Confidential 8
  9. 9. ‘Servicing customers all over the world’ 29 August 2013 Confidential 9
  10. 10. QPS’ Linearly Integrated Core Competencies Discovery/Candidate-Selection Stage Neuropharmacology, ADME and Tolerability Studies to support Drug Discovery Preclinical/Non-clinical Development Stage Animal Toxicology studies to support regulatory filing Development DMPK studies to support regulatory filing Regulated Bioanalysis to support animal toxicology studies Immunogenicity for PD and safety assessment Biomarkers for animal pharmacology studies PK/TK modeling Clinical Development Stage Phase I Healthy Volunteer studies Phase II to IV Patient studies Development DMPK studies to support NDA filing Regulated Bioanalysis to support clinical studies Immunogenicity for efficacy and safety monitoring PGx for patient stratification and efficacy monitoring Biomarkers 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’ 29 August 2013 Confidential 10
  11. 11. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 11
  12. 12. ‘helping you navigate your way through the screening and lead profiling of your CNS drug candidates’ NEUROPHARMACOLOGY 29 August 2013 Confidential 12
  13. 13. Global Neuropharmacology Services Brief Global Overview ‘Neuropharmacology services on the basis of scientific excellence and international quality standards’ In Vitro Neuropharmacology Profiling Neuronal Tissue Culture Mode of Action Full Safety Package In Vivo Neuropharmacology Profiling Transgenic and Non-transgenic Rats and Mice Generation / Phenotyping of new Transgenic Rat and Mouse Strains Screening for Efficacy Lead Profiling Molecular Biology, Biochemistry, Histology and Bioanalytics Full Safety Package 29 August 2013 Confidential 13
  14. 14. Global Neuropharmacology Services 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 Vitro Immunofluorescence Analysis 29 August 2013 Confidential 14
  15. 15. Global Neuropharmacology Services 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, AMD Oxidative 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 inhibitors Screening for acetylcholine and butyrylcholine esterase inhibitors 29 August 2013 Confidential 15
  16. 16. Global Neuropharmacology Services In Vivo Animal Models ‘High quality and cost effective lead profiling’ Key Competences (non-exhaustive list) Breeding Non-transgenic Mice and Rat Models MPTP (acute and chronic) induced Parkinson's disease MK-801-induced psychosis Forced swim test (depression) Scopolamine induced learning or memory recall impairments 6-OHDA induced injury of dopaminergic neurons Transgenic Mice and Rat Models All relevant transgenic models for Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) research available Various genetically modified animal models: FTD, Amyotrophic Lateral Sclerosis, Niemann Pick Disease and Huntington’s Disease Cross-breds of the different strains form complete models of human disease 29 August 2013 Confidential 16
  17. 17. Global Neuropharmacology Services 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 Data Biochemistry Data Histology Data 29 August 2013 Confidential 17
  18. 18. Global Neuropharmacology Services Molecular Biology ‘Our validated protocols for molecular biological assays allow for quantitative evaluations which fulfill the strictest guidelines’ Genetic Testing Generation of Expression Vectors for Transgenic Animals Generation of Stably Transfected Cell-lines Generation of Transgenic Mice Genotyping of Transgenic Animals by Quantitative PCR Analysis of Gene Expression by RT-PCR Quantification of Virus Particles by PCR Safety Monitoring for Gene Therapy 29 August 2013 Confidential 18
  19. 19. Global Neuropharmacology Services Biochemistry ‘Our GLP certified laboratory is ready to analyze all types of neurological biomarkers’ Bioanalysis in human blood or CSF samples Amyloid beta, tau and phospho-tau, alpha Synuclein Inflammation marker Enzyme activity: Cholinesterase, Monoaminooxidase and Myeloperoxidase Oxidative stress Cholesterol Analysis of disease related markers in brain, CSF, blood of Tg animal models; Assay Techniques: ELISA Western Blot Mesoscale Discovery Multiplex Assays Enzymatic assays Amorfix Aggregated Aβ Assay A4 (exclusively at QPS) 29 August 2013 Confidential 19
  20. 20. Global Neuropharmacology Services Histology ‘World-class quantitative histopathology services backed by a highly dedicated team of histology, pathology, neurobiology and image analysis experts’ Histotechniques According to principles of uniform, systematic random sampling Vibratome, cryotome or slide microtomes Immunohistochemistry Standard 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 imaging Z-stacking for high magnification Large data storage Quantifications Automated and semi-automated measurements Total comprehensibility of obtained data to images Customized quantification procedures and feasibility analyses 29 August 2013 Confidential 20
  21. 21. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 21
  22. 22. ‘helping you navigate your way through the biotransformation of your drug’ DMPK 29 August 2013 Confidential 22
  23. 23. Global DMPK Services Brief Global Overview ‘DMPK services include the necessary studies for regulatory filing at the appropriate time and mechanistic studies when required’ Pharmacokinetics Single and Multiple Dose, Dose Proportionality, Absolute Bioavailability, PK/TK Modeling Mass Balance/Excretion/Radiolabel Studies Formulation Optimization, Intestinal Permeability, other Mechanistic Studies Protein Binding; RBC/Plasma Distribution Partitioning Protein Covalent Binding Tissue Distribution Discovery QWBA Quantitative Whole-Body Autoradiography (QWBA) Micro-autoradiography (MARG) Metabolism Metabolic Stability, Species Comparison CYP450 Inhibition/Induction Metabolic Reaction Pathway Profiling Metabolite Profiling & Identification – In Vitro, Preclinical, and Clinical Rat PK 3-in-1 IV/PO 1 10 100 1000 10000 0 4 8 12 16 20 24 Comp'd #1(IV) Comp'd #1 (PO) Comp'd #2 (IV) Comp'd #2 (PO) Comp'd #3 (IV) Comp'd #3 (PO) 29 August 2013 Confidential 23
  24. 24. Global DMPK Services 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 Quality Each DMPK management team member has in-depth skill sets in different fields: Formulation & Absorption Pharmacokinetics & Protein Binding QWBA & Micro-autoradiography Metabolism Metabolite Identification Program Development Consulting Address routine and mechanistic ADME issues ADME Summary for Regulatory Submission 29 August 2013 Confidential 24
  25. 25. Global DMPK Services Discovery ADME Studies ‘QPS performs cost effective discovery ADME screens’ Metabolic stability CYP inhibition “Validated” process with FDA approved specific probe substrates and chemical inhibitors Protein binding Equilibrium dialysis using conventional device or RED or HT96 Rodent PK – linearly integrated Formulation In-life – Discrete or “N-in-1” dosing Bioanalysis method development & sample analysis “N-in-1” bioanalysis PK calculation Average turnaround time < 7.5 days from compound receipt to reporting of data 29 August 2013 Confidential 25
  26. 26. Global DMPK Services Candidate Selection Studies ‘QPS experienced staff knows how to select your best IND candidates’ Pharmacokinetics Formulation, dose proportionality Intestinal permeability Other mechanistic studies for absorption and disposition (or clearance) Metabolism Species comparison Metabolite profiling and/or identification Pilot CYP mapping Excretion Route of elimination – BDC studies Bile Duct-Cannulated Studies using 3H-labeled Compounds 0 10 20 30 40 50 60 70 80 90 100 110 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 # of Study %DoseRecovered Cage Wash Feces Urine Bile Average Recovery 87.4% Bile Duct-Cannulated Studies using 3H-labeled Compounds 0 10 20 30 40 50 60 70 80 90 100 110 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 # of Study %DoseRecovered Cage Wash Feces Urine Bile Average Recovery 87.4% 29 August 2013 Confidential 26
  27. 27. Global DMPK Services 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 oversight Eliminate the possibility of radiolabel degrading over an extended period of time between the two studies and the requirement of re-purification Increase efficiency using a single study protocol = ↓Study Cost Metabolite Profiling and Identification in the same study Both ion trap and quadrupoles tandem mass spectrometers for different MSn experiments Mass Balance Excretion Studies in Rats using 14C-labeled Cpds 0 10 20 30 40 50 60 70 80 90 100 110 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 # of Studies %DoseRecovered Carcass Air Cage Wash Feces Urine Bile Average Recovery 93.8% 29 August 2013 Confidential 27
  28. 28. Global DMPK Services 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 rooms 1 Surgical Suite Triple cannulated animals for special models & in situ CSF Intracranial infusions for up to 7 days Eight (8) bioanalytical labs for dose formulation, sample preparation, and analysis Mass Balance Studies Mass Balance Cages (Plastic and Glass) Micro-Filter Cages for Mice, Nude Mice and Rats In Vitro cell culture Lab S9, microsomes, and hepatocytes Tumor cell-lines for xenografts LIMS DEBRA and Watson 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 IV PO PO/BDC PercentDoseRecovered Rinse Urine Bile Feces 29 August 2013 Confidential 28
  29. 29. Global DMPK Services QPS Delaware DMPK Facility ‘DMPK function with all necessary equipment and self-contained for speed’ Two (2) Autoradiography Labs for Macro- and Micro-autoradiography Leica CM 3600 Cryomacrotome (whole-body) Leica Vibratome 9800 (whole-body) Leica CM 3050 S Cryomicrotome (individual organ/tissue) Molecular Dynamics Typhoon 9410 Imager Six (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 29 August 2013 Confidential 29
  30. 30. Global DMPK Services QPS Delaware DMPK Facility ‘DMPK function with all necessary equipment and self-contained for speed’ Dedicated LC/MS/MS Three (3) bioanalytical labs for sample preparation and analysis Six (6) Mass Spec (5 Sciex API 4000s, Finnigan LTQ ProteomeX) Waters UPLCs, Shimadzu VP-series LCs, Agilent 1100 LCs; LEAP HTC/PAL injectors Detectors – UV/Vis, Fluorescence, Electrochemical Tomtec Quadra 96 for 96-well sample preparation Radio-Quantitation Two (2) Packard Model 307 Sample Oxidizers Two (2) PE Tri-Carb 2800TR/2900TR Scintillation Counters PE TopCount® NXT Microplate Scintillation Counter Packard Cobra II Gamma Counter Four (4) Radioactivity Detectors ARC XFlow System; Off-line Fraction Collectors 29 August 2013 Confidential 30
  31. 31. Global DMPK Services QPS Delaware DMPK Facility ‘DMPK function with all necessary accreditation, certifications, permits, and licenses’ AAALAC Accreditation ABC License CDC Permit DEA Permit for Scheduled Control Substances (I-V) Federal Fish & Wildlife Permit NRC License for Radiochemicals 3H, 14C, 32P, 33P, 35S, 45Ca, 51Cr, 90Y, 99mTc, 111In, 125I, 188Re OLAW Assurance ORCA Certification USDA Permit 29 August 2013 Confidential 31
  32. 32. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 32
  33. 33. ‘helping you navigate your way through the safety of your drug’ Toxicology 29 August 2013 Confidential 33
  34. 34. Global Toxicology Services Brief Global Overview ‘QPS CTPS Taiwan is one of the most experienced toxicology centers in Asia’ Track Record Over 1000 GLP Studies conducted since 1997 17 dossiers compiled for US FDA IND submission 18 dossiers compiled for Taiwan IND submission Accreditations & Compliance: AAALAC Accreditation since 2000 Taiwan Accreditation Foundation (TAF) ISO 17025 Taiwan Department of Health (DOH) GLP OECD (TAF) GLP US FDA GLP compliance 29 August 2013 Confidential 34
  35. 35. Global Toxicology Services 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 Toxicology Genetic Toxicology General (non-GLP) Toxicity Testing Pharmacokinetics with Bioanalysis Biocompatibility Testing Topical Toxicity Testing 29 August 2013 Confidential 35
  36. 36. Global Toxicology Services General & Reproductive Toxicology ‘QPS CTPS is able to provide you with a comprehensive package of in vivo toxicology studies’ Single Dose Toxicity Studies Repeat Dose Toxicity Studies Up to 6 months in duration Routes of administration: oral, intravenous (injection and infusion), intramuscular, subcutaneous, intraperitoneal and others Animal species: mice, rats, guinea pigs, hamsters, rabbits, dogs ……….and cynomolgus monkeys coming soon! Reproductive Toxicology Fertility Teratology Animal species: rat and rabbit Clinical Pathology Urine Analysis Hematology Serum Chemistry Histopathology Tissue and Slide Preparation Tissue Image QA of Scanned Slides, Pathology Consultation and Evaluation by US Board-Certified Pathologist 29 August 2013 Confidential 36
  37. 37. Global Toxicology Services Genetic Toxicology ‘QPS CTPS is able to provide you a broad panel of in-house conducted genotoxicity tests’ Gene Mutation Assays Ames Test/Mini-Ames Test HPRT gene mutation assay In Vitro mouse lymphoma assay Cytogenetic Assays Sister chromatid exchange assay Chromosome aberration assay Micronucleus Assays Micronucleus assay in CHO cells and human peripheral lymphocytes Mouse micronucleus assay Cell Transformation Assay In Vitro cell transformation assay 29 August 2013 Confidential 37
  38. 38. Global Toxicology Services 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 Test Pyrogen and LAL Test Animal species: rabbit Intracutaneous Irritation Test Skin Sensitization Test Cytotoxicity Test In Vitro Hemolysis Mutagenicity Test Implantation Test 29 August 2013 Confidential 38
  39. 39. Global Toxicology Services 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 Studies Eye irritation test Dermal irritation test Animal species: rabbit Skin Sensitization Testing Buehler test Maximization test Animal species: guinea pig 29 August 2013 Confidential 39
  40. 40. Global Toxicology Services 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 SQA Large/small molecule, device development expertise On-site clinical pathology, histopathology by DACVP, dose analysis, bioanalytical Established global procedures for sample shipping and data analysis Remote 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 29 August 2013 Confidential 40
  41. 41. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 41
  42. 42. ‘helping you navigate your way through the measurement of your drug’ Bioanalytical 29 August 2013 Confidential 42
  43. 43. Global Bioanalytical Services Brief Global Overview ‘QPS is a global leader in bioanalysis for both small and large molecules’ Small molecules – using mass spectrometric techniques Large Molecules - using ligand binding assay techniques Global coverage of bioanalytical services with local presence in North America, Europe, India and Asia World 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 analysis Supporting a full range of development from Preclinical to Late Stage Clinical programs Immunogenicity & Neutralizing Antibody Activity Assessment Central Lab Services: Sample Logistics / Sample Repository / Preparation and Distribution of Sampling Kits 29 August 2013 Confidential 43
  44. 44. Global Bioanalytical Services 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) screening Toxicokinetic (TK) studies Clinical PK/Bioavailability studies Bioequivalency studies Therapeutic drug monitoring studies Biomarker studies Drug-drug interaction studies Sample Analysis of different compound structures: Oligonucleotides Analysis Peptide Analysis Sample Analysis in different biological matrices: Dried Blood Spots Tissues 29 August 2013 Confidential 44
  45. 45. Global Bioanalytical Services 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 Biosimilars Sample Analysis for different evaluation purposes: Pharmacokinetic (PK) screening Toxicokinetic (TK) studies PK/Bioavailability studies Bioequivalency studies Therapeutic drug monitoring studies Biomarker studies Drug-drug interaction studies Immunogenicity monitoring using four-tier approach: Screening Confirmatory (immunodepletion) Titer assessment (quantification) Cell-based neutralizing antibody detection 29 August 2013 Confidential 45
  46. 46. Global Bioanalytical Services ‘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 8/29/2013 Confidential 46 Elemental Analysis in Drug Development
  47. 47. Global Bioanalytical Services 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 Oligonucleotides Peptides Proteins Monoclonal Antibodies 29 August 2013 Confidential 47
  48. 48. Global Bioanalytical Services 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/MS 29 (25 Sciex API 4000 and 4 Sciex API 5000) Large Molecule ImmunoBioanalysis Capability in PK, Immunogenicity, NAb assay, and biomarkers Various technology platforms: ELISA, MSD ECL, GYROS and RIA Hundreds of validated methods (DDI CoMeds) available Complete list available on website (www.qps.com) WATSON LIMS System v7.4.1 with Immune Response Module (IRM) 29 August 2013 Gyrolab™ Automated Immunoassay Workstation Confidential 48
  49. 49. Global Bioanalytical Services 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/MS 8 Triple Quadrupoles Mass Spec (API 5500Q, 4000, 3000) Large Molecule ImmunoBioanalysis Capability 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 studies UV-Vis Spectrometry, determination of radioactive labeled compounds Hundreds of validated assay methods (DDI CoMeds) available Complete 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 24 July 2012 Confidential 49
  50. 50. Global Bioanalytical Services 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/MS 7 Triple Quadrupoles Mass Spec (2 Sciex API 3200 and 5 Sciex API 4000) Hundreds of generic methods available Complete list available on website www.qps.com QPS-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 estimation Bioequivalence analysis PK and PK/ PD analysis In Vitro - In Vivo Correlation (with Pharsight™ IVIVC toolkit software) WinNonlin™ for PK analysis and SAS for statistical analysis Final Report submissions in E3/ CTD format 29 August 2013 Confidential 50
  51. 51. Global Bioanalytical Services 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/MS 4 Triple Quadrupoles Mass Spec (4 Sciex API 4000) Large Molecule ImmunoBioanalysis Capability in PK, Immunogenicity, Nab Assay, and Biomarkers Hundreds of generic methods available Complete list available on website (www.qps.com) WATSON LIMS System v 6.4 (WATSON v7.4.1 Coming Soon!) 29 August 2013 Confidential 51
  52. 52. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 52
  53. 53. ‘helping you navigate your way through the efficacy of your drug’ Translational Medicine 29 August 2013 Confidential 53
  54. 54. 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’ Biomarkers PD protein or biochemical markers Various biomarker assay platforms (ELISA, Immulite®, Bioplex®, MSD® Imager 6000 ECL, GYROS, Flow Cytometry, LC-MS/MS and LC-ECD) Cell-based & functional assays Western Blot analysis & quantification Radioligand binding assay On-site cell stimulation and cytokine biomarker panel evaluation Pharmacogenomics (PGx) DNA & RNA isolation and banking Genotyping (SNPs, insertions, deletions, copy numbers, etc.) CpG methylation quantification RNA isolation & expression profiling (qRT-PCR) 29 August 2013 Confidential 54
  55. 55. 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 29 August 2013 Confidential 55
  56. 56. 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 Banking Genotyping (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 Quant Gene Expression Profiling in various matrices (qRT-PCR) Pyrosequencing 29 August 2013 Confidential 56
  57. 57. Global TLM Services 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 ECL Antibody Generation Critical Reagent Labeling Cell Based Neutralizing Antibody (NAb) Assays Cell Banking and Maintenance Technology Transfer Custom Method Development and Optimization Meso Scale Discovery 29 August 2013 Confidential 57
  58. 58. 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 ELISA Cell-Based Functional Assays, e.g. cell viability assay Other Functional Assays, e.g. activity assay Receptor Binding Assays 29 August 2013 Confidential 58
  59. 59. 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 Assays Pharmacodynamic (PD) & Safety Markers Multiplexing Genetic Markers (CYP450 TaqMan or Affymetrix DMET genechips) Pharmacodynamic (PD) Assays On-Site Cell Stimulation and Biomarker Analysis Fit-For-Purpose Biomarker Assay Development and Validation (various matrices) Protocol Design Standard Curves from Custom 6-Plex Cytokine Assay Concentration, pg/mL 1 10 100 1000 10000 signal 0 5000 10000 15000 20000 25000 IL-1ß IL-2 IL-4 TNF-a IL-6 INF-g Luminex™ 29 August 2013 Confidential 59
  60. 60. 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/MS BD FACS Canto II® Ultracentrifugation RIA Western Blot Analysis Radioligand Binding Assay (SPA) 29 August 2013 Confidential 60
  61. 61. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 61
  62. 62. ‘helping you navigate your way through the complex challenges of the early development of your drug’ Global Early Stage Clinical Research 29 August 2013 Confidential 62
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  64. 64. 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: 29 August 2013 Confidential 64 240 in Springfield, Missouri, USA 75 in South Miami, Florida, USA 20 in Hollywood, Florida, USA 92 in Hyderabad, India 40 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) studies Clinical PK/PD studies Drug-Drug Interaction studies Cardiac Safety/Thorough QT/QTc studies Bioavailability/Bioequivalence/ANDA studies Vaccine studies Specialty Populations Proof-of-Concept (PoC) in multiple therapeutic areas
  65. 65. Global Early Stage Clinical Research 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 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 29 August 2013 Confidential 65
  66. 66. Global Early Stage Clinical Research 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 Data Design and Preparation of the Trial Clinical Project Management Preparation of the Study Protocol, Informed Consent, and Case Report Forms Clinical Conduct Clinical Data Management Biostatistics Bioanalysis/Biomarker Assays Conduct PK/PD and/or Pop PK/PD Data Analysis and Modeling Prepare PK/PD Report Prepare and Publish Fully Integrated Clinical Study Reports Monitoring Pharmacovigilance 29 August 2013 Confidential 66
  67. 67. Global Early Stage Clinical Research 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 Campus Over 1000 studies completed since 1994 17 FDA Inspections Clinical Staff Experience 8+ years average length of employment Less than 3% staff turnover rate 37,000 subjects in database Specialty Studies Vaccine Postmenopausal Geriatric Birth Control and Birth Control Naïve Cardiac Safety/TQTc 29 August 2013 Confidential 67
  68. 68. Global Early Stage Clinical Research QPS MRA – South Miami, Florida, USA ‘QPS MRA conducts complex phase I studies that other sites are unable to execute’ 16,000 Square Feet facility 50 actively monitored beds Unique high-level medical oversight Healthy volunteers (FIM, SAD, MAD), specialty populations, and Proof-of-Concept (PoC) in multiple therapeutic areas Consistent high enroller, often exceeding contracted subject allocation Excellent subject retention (over 90%) 29 August 2013 Confidential 68 Specialty & PoC Populations Elderly Obesity Hepatic Insufficiency Parkinson’s Renal Insufficiency Depression Psoriasis Pediatric ADHD Type II Diabetes Arthritis Rheumatoid Osteoarthritis Post-Menopausal Lupus Hypertension On Demand
  69. 69. Global Early Stage Clinical Research 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. facility David Seiden, MD – Board-Certified in Sleep, Neurology, and Psychiatry Healthy 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-IV BRG Facility 20 beds 15 ACRP-Certified Coordinators, Nurse Practitioner, Neuropsychologist, RN’s, LPN’s, Sleep Technicians QA / Regulatory depts Laboratory, EEG, ECG, pulse oximetry recording equipment, polysomnography, refrigerators, centrifuge, freezers (-20 C and -70 C) 29 August 2013 Confidential 69
  70. 70. Global Early Stage Clinical Research 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-house ISO 9001:2008 certified organization Approved 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 2010 Over 630 conventional BA/BE studies conducted for various regulatory agencies (130 are pivotal studies) Twenty (20) products successfully approved by US FDA Clinical 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 Imaging NCE PK studies like Food Effect, Dose Proportionality and Drug-Drug Interaction 29 August 2013 Confidential 70
  71. 71. Global Early Stage Clinical Research 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-house Bioavailability / Bioequivalence Studies Healthy Normal Populations PK in Cancer Patient Populations Scaled Average Bioequivalence Conventional BA/BE studies conducted for various regulatory agencies More than 40 products successfully approved by Taiwan FDA 29 August 2013 Confidential 71
  72. 72. Global Early Stage Clinical Research 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 studies Fast and easy access to top-notch medical, clinical-pharmacological, medical and scientific expertise Parallel 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 time Logistically closely linked to the bioanalytical laboratory to enable fast turnaround of plasma concentration data of laboratory biomarkers and drug candidates Specialty Studies: 29 August 2013 Confidential 72 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 Medicine Imaging (PET, fMRI) studies Continuous) CSF sampling in Healthy Volunteers and (Alzheimer) Patients (Radiolabel (14C) Human Microdosing and Mass Balance studies
  73. 73. Slide Deck Navigator Navigate me directly to…. Global Neuropharmacology Services Global DMPK Services Global Toxicology Services Global Bioanalytical Services Global Translational Medicine Services Global Early Stage Clinical Development Services Global Phase II - IV Clinical Development Services Why QPS? 29 August 2013 Confidential 73
  74. 74. ‘helping you navigate your drug all the way across the finish line’ Global Phase II-IV Clinical Research 29 August 2013 Confidential 74
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  76. 76. 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 Management Clinical Trial Monitoring Clinical Trial Logistics and Supplies Data Management Biostatistics Medical Writing 29 August 2013 Confidential 76
  77. 77. Global Phase II-IV Clinical Research Phase II – IV Clinical Study Experience 29 August 2013 Confidential 77 Phase II 67 Studies Phase III 59 Studies Phase IV 63 Studies N = 189 Studies
  78. 78. Global Phase II-IV Clinical Research Top 10 Therapeutic Indications 29 August 2013 Confidential 78
  79. 79. Global Phase II-IV Clinical Research ‘Apart from stand-alone clinical research activities, QPS is also able to manage your entire clinical drug development program’ Clinical Consultancy and support through Project Life Cycle Design of Clinical Program and Individual Studies QPS will conduct your project according to the protocol with high quality data within timelines and within budget Project Management 29 August 2013 Confidential 79
  80. 80. Global Phase II-IV Clinical Research Site Management & Monitoring ‘Let QPS manage your Clinical Research Activities’ 29 August 2013 Confidential 80 Site Selection, Patient Recruitment and Site Logistics Site Training Study Reference Manual Protocol/Study Materials One-on-One Sessions Train-the-Trainer Sessions Online Presentations Online Tutorials for EDC EDC On-Site Monitoring Study Initiation Interim Visits Study Close Out Regulatory Document Collection, Review and Submission Site Audit and/or Qualification Per Request For Cause
  81. 81. Global Phase II-IV Clinical Research ‘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/Branches Clinical Database Paper based CRF eCRF Fast Data Base Lock Data Management 29 August 2013 Confidential 81
  82. 82. Global Phase II-IV Clinical Research Data Analysis for Late Stage Clinical Studies SAS Programming Exports of Tables, Figures and Listings (TFLs) PK / PD Analysis (including Pop PK) Pharmacokinetic and statistical consultancy Study design including optimization of PK sampling and power evaluation of population size enrolled Non-compartmental and compartmental PK modeling Population pharmacokinetics Stand-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 29 August 2013 Confidential 82
  83. 83. ‘QPS can take care of all your medical writing needs’ Clinical Study Protocol Investigator’s Brochure IMPD (Investigational Medicinal Product Dossier) ICF Scientific Publications Final Clinical Report (CTD or eCTD) Global Phase II-IV Clinical Research Medical Writing 29 August 2013 Confidential 83
  84. 84. Global Phase II-IV Clinical Research Clinical Advantages Global capabilities yielding significant cost savings Low turn-over of QPS staff, specifically CRAs Access to a large network of investigators Experienced central management and local expertise Personal touch of a boutique CRO but with global capabilities 29 August 2013 Confidential 84
  85. 85. 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 personnel Direct access to vast amounts of drug discovery & development experience Scientific expertise spanning preclinical work to drug approval Direct access to QPS’ people's hearts! Enthusiasm Professional attitude Flexibility in meeting client needs Focus 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 29 August 2013 Confidential 85

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