Hepatitis C Virus LabCorp Background and Capabilities

Hepatitis C Virus LabCorp Background and Capabilities Esoterix Clinical Trials Services (Esoterix) is a division of LabCorp, an independent clinical...
Author: Owen Lucas
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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