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Monogram Biosciences Pharma Collaborations -A LabCorp Center of Excellence –

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Presentation on theme: "Monogram Biosciences Pharma Collaborations -A LabCorp Center of Excellence –"— Presentation transcript:

1 Monogram Biosciences Pharma Collaborations -A LabCorp Center of Excellence –

2 Monogram Biosciences Founded as ViroLogic, Nov 1995, South San Francisco, CA Acquired by LabCorp as wholly-owned subsidiary, Aug 2009 ~225 employees Virology/Oncology Commercial Assays Clinical management Drug/vaccine development Clinical Reference Laboratory CLIA/CAP accredited Science directed Over 175 peer-reviewed publications Ranked highly for intellectual property portfolio Has conducted over 200 projects involving every commercially-available HIV antiretroviral

3 Monogram Biosciences A LabCorp Center of Excellence 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.

4 Monogram’s Technologies are Offered Directly at Monogram and through Esoterix Clinical Trials Services, a Division of LabCorp Central Labs Dedicated labs for clinical trials Cranford, NJ Mechelen, Belgium Beijing, China Singapore Broad, validated test menu Test method harmonization 8 Centers of Excellence Coagulation Endocrinology Oncology Infectious disease Anatomic pathology Molecular pathology Flow cytometry Small and large molecule Method development and validation LC/MS/MS Non-GLP discovery services Cell-based assays Discovery and development GLP biomarker services MS-based assays Global expertise: Cranford, NJ Mechelen, Belgium San Diego, CA West Trenton, NJ Discovery, development, commercialization FDA experience IVD Trial Participation Successful PMA submission 40,000 ft 2 biorepository Integrated Data Management Commitment to Quality Dedicated Project Management Bioanalytical Labs Biomarker Discovery Companion Diagnostics Esoteric Testing

5 Testing Services Across all Phases of Development Screening drug candidates Characterizing resistance Screening patients for enrollment Optimizing background therapy Characterizing treatment failure Defining clinical cut-offs Enhancing market positioning Discovery Preclinical Clinical Post-Marketing

6 HCV Testing Services

7 Monogram is designed to be a ‘one stop shop’ to meet virology testing needs for clinical trials Monogram is applying its legacy of providing accurate, high throughput HIV testing to HCV Current HCV assays NS3: Sequencing & Phenotyping NS5b: Sequencing & Phenotyping NS5A: Sequencing & Phenotyping IL28B SNP Genotyping Subtyping/Genotyping and Viral Load Deep sequencing and clonal analysis Monogram HCV Assays and Services

8 GenoSure® HCV – NS3/4a sequencing Monogram’s GenoSure HCV assay is now available for use in the clinic Designed to help determine patient susceptibility to the commercially available HCV drugs Validated to measure VL>2000 copies/ml

9 Monogram HIV Assays and Services for Clinical Research and Development Protease/Reverse Transcriptase Inhibitors PhenoSense® (phenotype) GenoSure ® MG (genotype) PhenoSense® GT≤ (combination phenotype/genotype) Entry Inhibitor Susceptibility (T20) GenoSure PRIme® – genotyping PR/RT and Integrase in a single assay Trofile ®, Trofile® DNA (Co-receptor Tropism) Integrase Susceptibility (phenotype; genotype) Assembly Inhibitor Susceptibility (phenotype; genotype) Replication Capacity & Sequencing Subtype Neutralizing Antibodies – for HIV and Influenza Clonal Analyses PhenoScreen ® Novel Drug Testing Database queries Viral Load (Roche COBAS/Ampliprep TaqMan 2.0, Abbott Real Time)

10 HIV PR/RT Resistance Testing

11 PhenoSense HIV Cell Assay TransfectionInfection Resistance Test Vector DNA A-MLV env DNA A Pseudovirions RT inhibitors added PR inhibitors added

12 Patient virus exhibits reduced susceptibility to the drug PhenoSense HIV Data Patient: Control:

13 GenoSure MG Report Monogram’s GenoSure MG report combines LabCorp’s genotyping capabilities (for faster turnaround), and Monogram’s proprietary algorithm…

14 Sequencing Resistance Mutations Prediction of Drug Susceptibility Interpretation Recombinant Virus Transfection Measure of Drug Susceptibility Infection Patient virus PR-RT DNA RT-PCR Resistance Test Vector Vector Assembly PhenotypeGenotype Bioinformatics Parallel Phenotype/Genotype Testing PhenoSense GT Assay (PSGT)

15 Drug Resistance Testing: Genotype vs Phenotype Benefits and Limitations Genotyping Generates viral sequence (population) Identifies virus mixtures mix of susceptible and resistant virus species example: K103K/N Major Limitation: Interpretation of complex mutational patterns or reliance on algorithm Immature algorithms for new agents

16 GenotypingPhenotyping Direct measure of susceptibility Ease of interpretation Demonstrates effect of complex combinations of mutations Resistance and Cross-Resistance Re-sensitization Partial Activity Replication Capacity Generates viral sequence (population) Identifies virus mixtures mix of susceptible and resistant virus species example: K103K/N Major Limitation: Interpretation of complex mutational patterns or reliance on algorithm Immature algorithms for new agents Drug Resistance Testing: Genotype vs Phenotype Benefits and Limitations

17 Parallel Phenotype/Genotype Testing PSGT Report – Examples of Discordance

18

19 Pol and Integrase Resistance Testing

20 Monogram’s proprietary Pol assay allows sponsors and investigators to cost- effectively genotype PR/RT and Integrase in a single assay Please contact Monogram for technical details on this assay GenoSure PRIme

21 Integrase Resistance Testing Monogram offers both genotyping and phenotyping to assist Integrase resistance in the clinical trial setting

22 HIV Tropism Testing

23 Transfection HIV env expression vector containing patient’s PCR- amplified HIV env fragments ++ HIV genomic luciferase vector CD4 + CCR5 + Infection CD4 + CXCR4 + virus entry inhibitors added B. A. C. D. E. F. The Trofile Assay

24 Trofile Report Trofile identifies the tropism of an individual patient's HIV strain – R5, X4, or a combination of these known as dual/mixed (D/M) Highly accurate, reproducible results using the complete HIV envelope (gp160) Clinically validated for selecting patients for CCR5 antagonist therapy

25 Trofile DNA Test Description: Cell-associated DNA isolated from PBMCs is incorporated into Monogram’s proprietary testing vector and run in a single-cycle recombinant assay to determine tropism. Product Specifications: Analytically validated to identify tropism in cell associated DNA. Sample Input: Whole blood; PBMC

26 Neutralizing Antibodies/Vaccine Development

27 Monogram Neutralization Assay

28 Three control viruses tested with every plasma: NL43 – neutralization sensitive lab strain JRCSF – well known primary isolate aMLV – specificity control: A test IC50 must >3X IC50 with aMLV to be called positive (green color) HIV+ Plasma Control: Tested with every virus in every run One control for every 7 sera tested N16, Z23 - Broad, low titered neutralizing capability Purpose of controls: Allow Monogram to assess run performance Allow PI to compare data across time Neutralization Assay Controls

29 JRCSF aMLV Negative curve - No inhibition of aMLV by 2G12 Positive curve - IC50 = 0.56ug/ml aMLV = specificity control Anti-HIV antibodies will not inhibit aMLV Antibody Neutralization Assay Inhibition Curve

30 Multiple formats: 1.HITS – 4 dilutions – For screening large numbers of sera – Report % inhibition at each dilution – 2.CURVES – 10 dilution curves with IC50, 80, 90, 95 – Cutoff for positive is >3X IC50 with aMLV 3.CURVES PLUS – 10 dilution curve and IC50, etc. plus % inhibition at each dilution Assay Formats

31 Other Virology Testing and Services

32 Novel Drug Characterization Monogram can leverage its virus library and database to construct panels for drug characterization

33 Oncology Testing Services: VeraTag technology and HERmark assay

34 How VeraTag Works What is a “VeraTag” (VeraTag Reporter)? Three components Recognition element (most often antibodies) Cleavable tether (thio-ether or disulfide bond) Fluoroscein reporters (variable mass-charge) antigen antibody tether fluoroscein

35 HERmark Assay

36 HERmark Assay Workflow

37 HERmark Report Classification of HERmark positive, negative, or equivocal Lab Developed Test Validated to CLIA standards Performed in a central, CAP-certified clinical reference laboratory All cases reviewed by Board Certified Pathologists

38 Additional VeraTag Assays

39 For questions about Monogram technology or assay ordering: Andrew Gale Director, Pharma Collaborations


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