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QPS Global Capabilities Presentation
 

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 ...

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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  • How do we as QPS introduce ourselves to you? The content of the presentation will be as follows:I would like to start sharing the core values of QPS with you and the values where we believe in, followed by the history, a brief overview of QPS and our global presence. QPS has 6 core competencies: DMPK, Tox, Bioanalysis, Translational Medicine, Early Stage and Phase II – IV Clinical DevelopmentAt the end of the presentation we would like to summarize what sets QPS apart and makes us different from other providers.As way of introduction, I would like to start by sharing the core values of QPS with you, along with the values that we believe in, followed by the company history, a brief company overview of QPS and our global presence. QPS has 6 core competencies: DMPK, Tox, Bioanalysis, Translational Medicine, Early Stage and Phase II – IV Clinical Development.In this presentation, I will be concentrating on our Bioanalysis, Early Stage and Phase II - IV Clinical Development capabilities.So why QPS?
  • As you can see in this slide, QPS began its history in the early 90’s, with the foundation QPS in Delaware in 95, and Xendo Drug Development here in Holland in 1999.At the begining of this century, QPS Taiwan was founded and in 2008 QPS acquired Bio-Kinetic; this was swiftly followed by the aquisition of Xendo Drug Development to create QPS-NL.Indeed in the last few years QPS has been very active with the aquisition of Qualitix & CTPS in Taiwan and Bioserve in India.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • Neuroharmacology is one of QPS’s core competencies. We have the ability to conduct all the studies that help screen and profile your CNS drug candidates.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • DMPK is one of QPS’s core competencies. We have the ability to conduct all the studies that help determine the biotransformation of your drug.
  • Our DMPK group is able to conduct all the studies needed for regulatory filing, including PK studies, protein binding, tissue distribution and metabolism studies. We can also do mechanistic studies that might be required for your program.
  • Our staff at QPS is our biggest asset. The senior team members within the DMPK group have an incredible amount of experience in pharmaceutical and biotech discovery and development. They also have significant CRO experience. Many of our team members were hand-picked for their specific area of expertise and skill sets.
  • We offer some cost-effective discovery screening options for metabolic stability, CYP inhibition, protein binding and rodent PK studies. We offer both discrete and cassette dosing.
  • We are experts at conducting important candidate selection studies (including PK, metabolism and excretion studies) and can offer guidance in selection of your best IND candidate.
  • QPS’s innovative and efficient combination study designs save time, money and radiolabeled material. This graph shows that over 45 studies, QPS achieved an average of almost 94% recovery of drug from mass balance excretion studies.
  • Our DMPK department has all its own equipment to enhance speed and efficiency. Our mouse and rat vivarium has 9 rodent room and 1 surgical suite. We have 8 bioanalytical labs for dose formulations, sample prep and analysis and a cell culture lab for S9, microsomes, hepatocytes and tumor cell lines for xenografts.
  • We have 2 autoragiography labs for macro- and microautoradiography. Our autoradiography labs are outfitted with all the equipment needed for freezing carcasses or tissues, slicing, mounting, staining, imaging and analyzing the tissue slices.
  • This slide lists all the equipment in the DMPK labs dedicated for LC/MS/MS and for radio-quantitation.
  • QPS DMPK functions with all the necessary accreditations, certifications and licenses needed to conduct your studies per regulatory requirements.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • QPS Holdings added toxicology to the stable of service offerings by acquiring CTPS in late 2010 to establish QPS-CTPS Taiwan. CTPS DCB had been in operation since 1984.
  • As an off shore provider of toxicology services to the pharmaceutical and biotech industries QPS-CTPS brings to the table an impressive record of accreditations, compliance and submissions. Over 1000 GLP studies have been conducted in support of a total of 25 dossiers compiled for either US FDA or Taiwan submission.
  • The core competencies of QPS CTPS as listed above focus on those areas that characterize drug development, medical device, dermatology and cosmetic product safety concerns. In all areas, preliminary safety questions can be also addressed from a non-regulated perspective to support candidate selection..
  • The general and reproductive toxicology capabilities QPS CTPS can be packaged and tailored to meet client needs in of support IND and NDA submission filings (based upon therapeutic area and need ). This slides illustrates those capabilities ranging from single dose toxicity to reproductive toxicology. Supporting services for these studies include clinical pathology and histopathology.
  • Genetic Toxicology is an integral component of the regulatory IND submission package. Our genetic toxicology services are potentially predictive to categorize genotoxic agents to humans.  These assays support results of other studies in the IND package, providing the basis for regulatory decisions and even discovery assessment.
  • QPS-CTPS also provides a wide range of studies in the biocompatibility area to assess the toxicity potential of medical devices for cytotoxicity, sensitization, and irritation. The types and number a studies conducted is dependent upon regulatory requirements and product claims.
  • Primary eye and dermal irritation studies have been conducted over the years in support of registrations in the cosmetic and dermatology industries. In-vivo skin sensitization is utilized to identify skin sensitizers effectively. QPS-CTPS offers what is considered the standard battery of testing services to meet these industries needs.
  • Primary eye and dermal irritation studies have been conducted over the years in support of registrations in the cosmetic and dermatology industries. In-vivo skin sensitization is utilized to identify skin sensitizers effectively. QPS-CTPS offers what is considered the standard battery of testing services to meet these industries needs.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • As mentioned at the begining of he presentation, today I would like to concentrate on the clinical development stages and begin with our expertise in Bioanlysis helping you to navigate your way through the measurement of your drug.
  • At QPS we are proud to be a world leader in Bioanlysis for both small and large molecules.Using mass spec techniques in small molecule and ligand binding assays in large molecules – we use other tecniques as well which I will go into morer detail in the next few slides.As pointed out we have global coverage in our bioanalytical services – with over 150 technical staff, and state of the art equipment like the API5500., a capacity of over 45 mass specs and capabilities extending from LC-MS, LBA and hybridisation ELISA.We have an extensive and growing library of validated assays - 750 plus, and we can support a full range of development from pre-clinical to late stage programs.We are very proud of our rapid assay development and validation, our Immunogenecity capabilities and our Central Lab service providing sample logistics, sample repository and the distribution of sampling kits.
  • If I may, I would like to go into greater detail on our capabilities in Small Molecule LC-MS/MS.QPS is a global leader in Bioanlysis, and is able to analyse samples from a wide range of different studies , compounds and biological matrices.We offer method development and validation and sample analysis as required for differing evaluation purposes, including, but not limited to PK screening, tox studies, bioequivalency studies, biomarker studies and drug-drug interaction studies.We can analyse different compound structures such as Oligonucleotides and peptides, and use different biological matrices such as tissue samples and Dried Blood Spots.
  • We are also very proud of our capabilities in Large Molecule Immunobioanalysis. As with our small molecule service, we offer method development and validation, and analysis for various requirements, including but not limited to PK screening, Tox studies, biomarker and drug-drug interaction studies.We approach Immunogenecity monitoring in four tiers: Screening, confirmatory – looking at immunodepletion - , Titre assessment and cell-based neutralising antibody detection.
  • We also have excellent capabilities in Elemental Analysis in biological matrices.We are a unique provider of GLP trace and ultra-trace elemental analysis by ICP-MS.This is a technique being increasingly applied to the metabolism and PK/PD of metal and non-metal analytes – be they pre or actual clinical studies.These applications developed using ICP-MS here at QPS include but are not limited to Platinum in plasma and urine for chemotherapies and new investigational compounds;Gadolinium for supporting studies with MRI contrast reagentsAnd Magnesium, Calcium and Phosphates in food and faeces supporting a mass balence study of a new phosphate binder.
  • We here at QPS are particularly pleased with the work being undertaken on the bioanalysis of Large Molecules using LC-MS/MS.We believe strongly in this novel application and can share some stunning results with you.We have undertaken method development and validation and sample analysis with Oligonucleotides, Peptides, Proteins and mono-clonal antibodies.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • QPS’ TLM capabilities are a key core competency. TLM is a growing , innovative, and vital area within QPS. With the increasing number of biotherapeutics, this is an important area especially with the implementation of new guidelines of FDA for PK for large molecule, ADA, PGx, & BMs.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • What I would like to do now, is to go into a little more detail about our capabilities in Early Stage Drug Development
  • QPS is a global leader in early stage clinical development and has one of the worlds largest Phase I capabilities, offering 400 beds over 3 continents – 240 in the USA, 92 in India, 40 in Taiwan and 24 and growing here in Groningen.QPS offers a broad spectrum of study types - the more complex first in man SAD, MAD and food effect studies here in the Netherlands. Also in Groningen we offer Human mass balence studies, microdosing studies and Imaging studies using PET and MRI – I will go into greater detail on these capabilities in a few slides time.We also undertake PK/PD and drug-drug interaction studies not only here in Groningen but aslo at our facilities in the USA, India and Taiwan.Thorough QT studies for cardiac safety are undertaken at our US sites, while our capabilities in Bioavailability, Bioeqivalence and ANDA studies can be taken at any of out US, Indian and Taiwanese sites depending on client requirementsBackground notes:Microdosing (or micro-dosing) is a technique for studying the behaviour of drugs in humans through the administration of doses so low ("sub-therapeutic") they are unlikely to produce whole-body effects, but high enough to allow the cellular response to be studied. [1]) This allows us to see the Pharmacokinetics of the drug with almost no risk of side effects. This is called a Phase 0 study and is usually conducted before clinical Phase I to predict whether a drug is viable for the next phase of testing. Human Microdosing aims to reduce the resources spent on non-viable drugs and the amount of testing done on animalsAbbreviated New Drug Application (ANDA).
  • QPS is a full service early stage CRO – not only providing exceptional Phase I capabilities but also the full back and front services neccessary.These include the review of pre-clinical data, the design and preparation of the trial including study protocol, informed consent and case report forms.We undertake project and data management, clinical data management and biostatistics. Full bioanalysis at our own labs along with report writing, monitoring and pharmacovigilance.
  • As I mentioned in ourearlier slides, our QPS Netherlands site is particularlysuitedto the first in man and more complex phase I programs.First key point is that we are hospitalbasedPhase I unit. We have completed over 100 studies – 20 first in man, worthnotingthat 12 of these wereusingbiologics.We have completed 7 PET studies and 6 oralcontraceptiveinteraction studies and have 2 recent FDA audits.One of the keyattributes of QPS is fastand easy access to first class medical, clinicalpharmacologicalandscientific expertise.Parallel submissionsto the competent authorityandethicalcommittees means here at QPS Groningen, we canobtain trial approval in 14 days. In addition, oursubstatialammendnentstimeline is only 48 hoursand 24 hoursfordoseescslation.As mentioned the very close proximity of ourbioanlytical labs enables a veryfastturnaroundforkey data.Here at Groningen we are particularly keen on ourcapabilitiestoperform more complex specialityPhase I studies.These includemulti-purposeumbrella protocols whereyoumay combine SAD MAD and food effect; female health oralcontraceptioninteraction studies andlactation studies.We have validatedneuropathicand acute pain models – and I will go into more detail in a minute on our Imaging – PET & MRI capabilities.Likewise we are veryexcitedwithourwork on CSF sampling in healthyvolunteers– towhich I have a dedicated slide to show you in a minute.Finaly we are very keen toundertakeyour carbon 14 massbalence studies.
  • The tag line of QPS is ‘Helps You Navigate”. By use of this slide dek navigator we will navigate you directly your service of interest
  • What is particularly exciting about our Pharmacology Unit here in Holland, is our commitment to innovation and to increasing our core capabilities
  • Our QPS site management and monitoring teams have got years of experience in providing high quality data and patient enrolment rates to your project.We have experience in Phase I to IV project management, and phase II to IV study management.We undertake clinical trial monitoring – including Phase I as well as logistics and supply.We are experts in Biometrics, PK/PD modeling and we are particularly experienced in the field of medical writing.Due to our extensive global reach we also highly proficient in managing in or out sourcing of clinical professionals.
  • Looking at the program, project and study management aspects, QPS, apart from stand-alone clinical research activities, is able to manage your entire clinical drug development program.We have a clinical consultancy to take care of the design of the program and the design of the individual studies ranging from Phase I right through to Phase IV.Key will be our experience and expertise in the budget, resource and timeline control so vital to a healthy outcome.Finaly we have extensive experience in a number of therapeutic areas, including but not limited to, Allergy, CNS, Oncology, Multiple Sclerosis and Radiology.
  • Looking in more detail at our site management and monitoring capabilities, QPS is able to take a lot of the research activities away from you….we can do the site selection, all site training needs including study materials and online EDC training;We undertake all site recruitment and on-site monitoring, as well as quality reviews of the data.We can undertake site audits from initiation to study close-out or if a due cause is identified.Finaly QPS will collect all essential documentation, perform all regulatory submissions and any site logistics required,
  • Our Biostatistics team has access to state of the art trial management and electronic data capture systems to deliver a truly first rate biostatistics service to your company.They undertake data analysis for late stage clinical studies, they are experts in SAS programming and the export of any tables and listings as required.For your PK/PD analysis needs, including population PK, QPS can offer a pharmacokinetic and statistical consultancy; study design and statistical power evaluations, any modelling requirements, as well as population PK and stand-alone PK/PD reports.As usual at QPS, we have extensive experience in a number of indications including but not limited to various Phase I indications, vascular surgery, cardiology and CNS.
  • Likewise our Medical writing capabilities where QPS can take care of all of your needs, right from study protocol, Investigator brochures, the IMPD dosier, scientific manuscripts, through to the final clinical report – paper or electronic – and of course experience in a number of therapeutic indications.Background:ICF : International Classification of Functioning
  • What also may be of significant interest to you is our temporary staffing and flexible sourcing solutions.We would be delighted to have QPS employees brought temporarily onto your drug development team in any one of a number or areas.These could be in the area of clinical research associates or coordinators, project managers, regulatory staff, through to biostatisticians, medical writers of research trainers.The key point here is that QPS is highly flexible to meet your unique drug development requirements.

QPS Global Capabilities Presentation QPS Global Capabilities Presentation Presentation Transcript

  • Find out how to achieve your next development milestone ahead of time www.qps.com
  • 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
  • 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
  • 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
  • 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
  • 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
  • History Confidential 729 August 2013
  • 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
  • ‘Servicing customers all over the world’ 29 August 2013 Confidential 9
  • 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
  • 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
  • ‘helping you navigate your way through the screening and lead profiling of your CNS drug candidates’ NEUROPHARMACOLOGY 29 August 2013 Confidential 12
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘helping you navigate your way through the biotransformation of your drug’ DMPK 29 August 2013 Confidential 22
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘helping you navigate your way through the safety of your drug’ Toxicology 29 August 2013 Confidential 33
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘helping you navigate your way through the measurement of your drug’ Bioanalytical 29 August 2013 Confidential 42
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘helping you navigate your way through the efficacy of your drug’ Translational Medicine 29 August 2013 Confidential 53
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘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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  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • ‘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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  • 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
  • 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
  • Global Phase II-IV Clinical Research Top 10 Therapeutic Indications 29 August 2013 Confidential 78
  • 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
  • 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
  • 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
  • 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
  • ‘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
  • 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
  • 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