Hepatitis C Virus LabCorp Background and Capabilities
Esoterix Clinical Trials Services (Esoterix) is a division of LabCorp, an independent clinical laboratory LabCorp’s Platform 220,000 customers 31,000 employees 1,500 patient centers 440,000 samples per day 40 years
Our mission is to be a leading provider of high science laboratory services that support clinical decision-making, enhance the management of laboratory information, and improve patient care.
Esoterix is a leading provider of laboratory testing for clinical trials Central Labs
Dedicated labs for clinical trials Cranford, NJ Mechelen, Belgium Beijing, China Singapore Broad, validated test menu
Biomarker Discovery
Esoteric Testing
Bioanalytical Labs
8 Centers of Excellence
Small and large molecule
Discovery and development
Coagulation Endocrinology Oncology Infectious disease Anatomic pathology Molecular pathology Flow cytometry
Method development and validation
GLP biomarker services
Companion Diagnostics
Discovery, development, commercialization FDA experience
MS-based assays IVD Trial Participation
LC/MS/MS Non-GLP discovery services Cell-based assays
Global expertise: Cranford, NJ Mechelen, Belgium San Diego, CA West Trenton, NJ
Successful PMA submission 40,000 ft2 biorepository
Test method harmonization
Commitment to Quality
Integrated Data Management
Dedicated Project Management
Esoterix has unique qualifications to support clinical trials Scientific Expertise
Global Scale and Logistics
Relevant Experience
Near Patient Testing
Comprehensive test menu
27 sites on 5 continents
4,300 studies
1,500 patient centers
8 Centers of Excellence
Clearstone acquisition provides wholly owned labs in China and Singapore
840 international studies
Large courier network
725 active trials
Economies of scale
Dedicated development and validation resources
PBMC networks
Data mart with over 1.2MM clinical results daily Biomarker co-prevalence Protocol design
49,000 sites Able to cost effectively deliver a sample globally
Data Analytics
Standardization of analytics and IT systems
25 years CT experience Companion diagnostic co-development
Unique model for Ph I/II and Ph IIIb/IV studies
Identification of investigators Patient recruitment Scientific data queries
Global network - 27 labs on 5 continents
Dedicated central labs have the broadest test menu in the industry Broad validated test menu Cranford, NJ 57,897 sq ft
Mechelen, Belgium 33,000 sq ft
•
Comprehensive safety/monitoring labs
•
Automated high throughput test systems
•
Proteins, nucleic acids, cell analysis
•
Logistics hub for LabCorp centers of excellence
•
Custom sponsor specific method validation
Test method harmonization Beijing, China 25,000 sq ft
Singapore 7,000 sq ft
•
Testing standardized on same platforms
•
Global ranges in place for over 80 analytes
•
Monthly global inter-lab proficiency testing
•
Correlation studies where needed
Global study support •
Single global database
•
Global project management services
•
Global data management
HCV Experience and Capabilities
HCV Experience LabCorp has a strong heritage in the support of HCV clinical development programs • Leading global laboratory provider of HCV therapeutic trials – Multiple global, pivotal interferon trials – Ongoing Direct-Acting Antiviral (DAA) studies • Supported multiple HCV diagnostic clinical trials • Close interactions with manufactures of HCV test kits/reagents to optimize and validate performance • First reference laboratory to launch HCV genotyping assay for strain typing • First reference laboratory to commercialize HCV PCR viral load testing • First reference laboratory to commercialize real time PCR HCV viral load assays • First and most sensitive (2 IU/mL) molecular qualitative assay for HCV (National Genetics Institute) • Proprietary serum pooling technology for pre-seroconversion viral screening (NGI)
Summary of HCV Assays
• • • • •
Genotype and Phenotype Resistance Testing IL28b Genotype/Subtyping Viral Load HCV diagnosis, quantitation and blood screening – UltraQual, SUPERQUANT & QuantaSure assays • Fibrosis: FibroSure • Standard liver function testing • Bioanalytical, Immunoanalytical, Biomarker
HCV Resistance Assays Monogram Biosciences • Monogram Biosciences is a LabCorp Center of Excellence focused on Virology and Infectious Disease – A leader in antiviral drug resistance testing – Resistance testing for all approved HIV drugs since 2000 – Science driven: 50 peer-reviewed publications and conference presentations annually
• Monogram has developed genotype and phenotype resistance assays for the three lead targets of HCV direct acting antivirals (DAAs) – NS5B: the polymerase that catalyzes the synthesis of new RNA early in the HCV replication process
– NS3/4A: the protease that catalyzes the cleavage of newly formed HCV polyprotein during the replication process – NS5A: a factor crucial to the formation of the replication complex and other aspects of the HCV life cycle
Example of Genotype Resistance Data
Sequence Analysis Client:
Example Report
NS5B population sequence analysis MGRM ID
MGRM GT
06-0293-BC 06-0294-BC 06-0298-BC 06-0300-BC 08-0742-HB 08-0743-HB 08-0762-HB 08-0769-HB 08-0790-HB 08-0793-HB
1a 1a 1a 1a 1b 1b 1b 1b 1a 1b
NS5B predicted amino acid differences from reference sequence (1b Con1, 1a H77)
GeneSeq® HCV NS5B Assay Project: Example Report
S5T, V11V/I, A15A/V, C46S, S90D, K98R, A117N, L184Q, R300Q, Q309R, N444D, S473S/T, S506N, L536L/I, G543S, R544Q, T552T/M, H566R, L588Y A117S, K212R, G376D, S431G, N444D, S506N, R544Q, H566R C46S, D66D/G, C110S, V116I, A117N, K124N, S189S/N, K212G, R270K, R300K, Q309R, A327Q, V405I, F415Y, I434M, N444D, S506N, R517K, I520V, G543S, R544Q, H566R A117N, K212R, S335N, N444D, G480S, S506N, R531K, G543S, F574L A15S, T19S, L36M, L47Q, M71V, R98K, A210S, N231S, V235T/I, T267F, A300S, E333A, A338V, K355Q, V499A, R510K, T520L, K523R, S549S/G T19S, N35G, L36M, V37I, L47Q, K106K/R, V116I, T130S, V147I, N206K, A210S, N231S, I262V, A300T, E333A, A338V, K355Q, E357A, S476T, G480S, V499T, R510K, T520I, A15S, T19S, L36M, L47Q, M71V, R98K, D135S, I138V, A210S, N231S, V235V/I, A252A/V, I262V, T267F, A300S, E333A, A338V, K355Q, M414M/L, V499A, S506N, R510K, Q5 T19S, L36M, L47Q, L57Q, K81R, R98R/K, S113S/G, T130S, A210S, N231S, A246A/T, I262V, A300T, E333A, A338V, K355Q, A421V, I424I/V, M426L, C451N/T/Y/S, S487A, V4 S5T, V11I, Q47L, A117N, L184I, S210A, R300Q, Q309R, N444D, R531R/K I11V, T19S, L36M, L47Q, A73V, A210S, C213N, A218S, A300S, C316H, V321I, E333A, A338V, K355Q, R510K, R531K, Q544R, S549G, S556S/G, L564V, R566H, W574L
Scientific Leadership
IL28B, Genotype/Subtype and Viral Load • IL28B – Assay profiles the rs12979860 SNP (3kb upstream of the IL28B gene) for CC, CT and TT genotypes using realtime PCR from blood or buccal swab samples • Genotype/Subtyping: Types 1-6 – Bayer Diagnostics Versant HCV 2.0 (LiPA) • Viral Load – Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test
Additional Capabilities • HCV diagnosis, quantitation and blood screening (National Genetics Institute) – UltraQual, SUPERQUANT & QuantaSure assays • Fibrosis: FibroSure – A patented artificial intelligence algorithm predictive of fibrosis and necroinflammatory activity in the liver • Standard liver function testing
Early Discovery / Preclinical Services Tandem Labs
Services
• Bioanalytical Small Molecules – Over 35 LC/MS/MS systems – Method development, method validation, sample analysis – GLP and non-GLP preclinical – Clinical • Non-GLP Bioanalytical & Biomarker – Discovery PK – GLP (Q2 2009) and non-GLP preclinical – Metabolite Profiling & ID – Biomarker Discovery, Pathway ID and Quantitation • Immunoanalytical & Biomarkers – GLP – ELISA, ECL – multiplexed, cell based assays
Summary LabCorp provides clients with: •
Proven experience in supporting sponsors’ HCV development needs
•
Broad menu of all major tests critical for the assessment of HCV
•
Robust scientific capability with active research in
resistance/phenotyping and technical evaluation programs with major IVD manufactures •
Global reach and logistics support with 27 sites and staff on 5 continents