monogram biosciences pharma collaborations -a labcorp center of excellence –

Monogram BiosciencesPharma Collaborations

-A LabCorp Center of Excellence –

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

Monogram BiosciencesA LabCorp Center of Excellence

LabCorp’s Platform220,000 customers 31,000 employees

1,500 patient centers 440,000 samples per day40 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.

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, NJMechelen, BelgiumBeijing, ChinaSingapore

Broad, validated test menu

Test method harmonization

8 Centers of Excellence

CoagulationEndocrinology OncologyInfectious 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, NJMechelen, BelgiumSan Diego, CAWest Trenton, NJ

Discovery, development, commercialization

FDA experience

IVD Trial Participation

Successful PMA submission

40,000 ft2 biorepository

Integrated Data Management

Commitment to Quality

Dedicated Project

Management

Bioanalytical Labs Biomarker Discovery

Companion Diagnostics

Esoteric Testing

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

HCV Testing Services

• 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

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

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)

HIV PR/RT Resistance Testing

PhenoSense HIV Cell Assay

Transfection Infection

Resistance Test Vector DNA

A-MLV env DNA

+

293-A

PseudovirionsRT inhibitors addedPR inhibitors added

Patient virus exhibits reduced susceptibility to the drug

PhenoSense HIV Data

Patient:Control:

GenoSure MG Report

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

Sequencing

Resistance Mutations

Prediction of DrugSusceptibility

Interpretation

Recombinant VirusTransfection

Measure of Drug Susceptibility

Infection

Patient virus

PR-RT DNA

RT-PCR

Resistance Test VectorVector Assembly

Phenotype Genotype

Bioinformatics

Parallel Phenotype/Genotype TestingPhenoSense GT Assay (PSGT)

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

Genotyping Phenotyping

• 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

Parallel Phenotype/Genotype TestingPSGT Report – Examples of Discordance

Parallel Phenotype/Genotype Testing

PSGT Report – Examples of Discordance

Pol and Integrase Resistance Testing

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

Integrase Resistance Testing

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

HIV Tropism Testing

Transfection

HIV env expression vector containing patient’s PCR-

amplified HIV env fragments

++HIV genomic

luciferase vector

CD4 +CCR5 +

Infection

CD4 +CXCR4 +

virus entryinhibitors

added

B.

A.

C.

D.

E.

F.

The Trofile Assay

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

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

Neutralizing Antibodies/Vaccine Development

U5gag

polP

P

R A+

U3

env

luciferase

R

U87:CD4/CCR5/CXCR4

Neutralization Assay:

Incubation with antibodies or patient plasma

Y

Y

YY Y

Y Y

env

lucgag

pol

P A+

a/b c/d

gp120 gp41

(patient env gene)

HEK-293

Vectors:

Clone population of viralenv present in plasma, cell culture, etc.

Drug resistant PR/RT can be used for testing plasmas with RT inhibitors

Monogram Neutralization Assay

• 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

JRCSF aMLV

Negative curve - No inhibition of aMLV by 2G12

Positive curve - IC50 = 0.56ug/ml

aMLV = specificity controlAnti-HIV antibodies will not inhibit aMLV

Antibody Neutralization AssayInhibition Curve

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

Other Virology Testing and Services

Panel # AMP IDV NFV RTV SQV LPV L10 K20 L24 D30 V32 L33 M36 M46 I47 G48 I50 F53 I54 A71 G73 V77 V82 I84 N88 L901 14.6 250.0 148.7 275.0 96.5 201.2 1 0 1 0 0 1 0 0 0 0 0 0 1 1 1 1 1 0 0 12 10.6 46.9 109.8 275.0 58.4 58.7 1 1 0 0 0 1 1 0 0 0 0 1 1 1 0 0 1 0 0 13 13.2 45.0 50.1 28.5 61.3 11.6 1 0 0 0 0 0 0 1 0 0 0 0 0 0 1 1 0 1 0 14 5.1 48.1 51.9 123.7 39.7 nt 1 0 0 0 0 0 0 1 0 0 0 1 1 1 1 0 1 0 0 15 6.3 31.1 21.0 79.2 20.0 nt 1 0 0 0 0 0 0 1 0 0 0 0 0 1 0 1 1 1 0 16 13.1 11.9 21.5 141.9 15.2 49.6 1 0 1 0 0 1 0 1 0 0 0 0 1 1 0 0 1 1 0 07 8.9 10.6 35.1 191.5 83.2 nt 0 0 0 0 0 0 1 0 0 0 0 0 1 1 0 0 1 1 0 18 2.1 23.6 23.1 42.2 143.1 nt 1 0 0 0 0 0 0 0 0 1 0 0 1 1 0 1 1 0 0 19 12.2 39.5 55.8 29.0 52.9 nt 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 110 5.5 151.2 91.0 79.9 561.7 60.8 1 1 0 0 0 0 1 0 0 1 0 0 1 1 0 0 1 0 0 011 28.8 250.0 74.2 275.0 550.0 148.8 1 0 0 0 0 1 0 1 0 1 0 1 1 1 0 1 1 0 0 012 4.2 82.6 98.1 116.5 596.6 nt 1 0 0 0 0 0 0 0 0 1 0 0 1 1 0 1 1 0 0 113 17.7 35.8 93.8 275.0 33.8 68.4 1 0 0 0 0 1 1 1 0 0 0 0 1 0 1 0 1 0 0 114 10.4 40.6 97.7 78.1 113.7 68.9 1 0 0 0 0 1 1 1 0 0 0 0 0 1 0 0 0 1 1 115 31.6 58.6 85.0 275.0 550.0 nt 1 0 1 0 0 0 0 1 0 1 0 0 1 1 0 1 1 1 0 016 16.7 11.2 53.5 275.0 69.0 nt 1 1 0 0 0 1 1 1 0 0 0 0 1 1 0 0 1 1 0 117 48.8 14.5 32.5 275.0 36.3 nt 1 1 0 0 0 1 1 0 0 0 0 0 1 0 0 0 1 1 0 018 20.5 20.3 30.1 275.0 27.4 97.1 1 0 0 0 0 1 0 1 0 0 0 0 1 1 1 0 1 1 0 119 2.8 169.2 167.2 89.2 550.0 72.1 1 1 0 0 0 0 1 0 0 1 0 0 1 1 0 0 1 0 0 020 29.6 250.0 297.4 275.0 550.0 156.0 1 1 0 0 0 0 1 1 0 0 0 0 1 0 1 0 0 1 0 121 7.7 27.7 20.0 107.6 4.9 22.3 1 0 0 0 1 1 0 1 0 0 0 0 0 1 0 0 1 1 0 122 42.1 16.9 50.1 275.0 127.6 93.0 1 0 0 0 0 1 0 1 0 0 0 0 1 1 0 0 1 1 0 123 4.9 23.2 41.5 59.5 61.3 nt 1 0 0 0 0 0 1 0 0 0 0 0 1 1 0 0 0 1 0 124 9.0 15.0 30.6 169.2 53.6 nt 1 0 0 0 0 0 0 0 0 0 0 0 1 1 0 1 1 1 0 125 3.3 10.2 39.4 40.2 1.0 6.1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 0 126 14.6 38.3 55.9 22.8 24.1 nt 1 0 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 1 0 027 7.0 35.9 64.7 44.4 96.7 13.8 1 1 0 0 0 0 1 1 0 0 0 0 0 0 1 0 0 1 0 128 130.0 22.5 29.4 275.0 550.0 273.1 1 1 0 0 0 1 1 0 0 1 1 0 1 0 0 0 1 0 0 029 13.8 40.8 58.2 132.9 94.4 67.3 1 1 0 0 0 0 1 1 0 0 0 0 1 1 0 0 1 1 0 030 7.0 12.7 30.5 87.3 46.6 38.2 1 0 1 0 0 0 1 1 0 0 0 0 1 0 0 0 1 1 0 031 10.1 20.2 40.1 80.0 74.5 nt 1 0 1 0 0 0 1 0 0 0 0 0 1 1 0 0 0 1 0 032 22.2 55.1 185.9 275.0 226.2 nt 1 1 0 0 0 1 1 0 0 0 0 1 1 1 1 0 1 0 0 133 14.3 25.5 54.5 217.4 68.6 nt 1 0 1 0 0 0 1 1 0 0 0 0 1 1 0 0 1 1 0 034 40.9 28.7 100.7 63.5 96.1 66.5 1 0 0 0 0 1 0 1 0 0 0 0 1 1 0 0 0 1 0 135 11.2 250.0 155.0 275.0 550.0 nt 1 1 0 0 0 0 1 1 0 1 0 0 1 1 0 0 1 0 0 136 12.5 6.7 18.5 60.1 9.5 51.5 1 1 0 0 0 0 1 0 0 0 1 0 1 1 0 0 1 0 0 037 4.9 12.3 13.1 81.7 25.4 nt 1 1 0 0 0 0 0 0 0 0 0 0 1 1 0 0 1 1 0 138 42.5 64.0 215.6 275.0 348.2 149.6 1 1 0 0 0 1 1 1 0 0 0 0 1 1 0 0 1 1 0 139 4.9 10.6 24.4 54.2 68.2 nt 1 1 0 0 0 0 0 0 0 0 0 0 1 1 0 1 1 1 0 140 15.0 11.4 52.0 42.4 126.7 nt 1 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 1 0 141 14.1 21.5 74.2 66.1 170.2 15.6 1 0 0 0 0 0 0 1 0 0 0 0 1 1 1 1 0 1 0 142 28.2 20.5 69.3 149.2 101.6 65.2 1 0 1 0 0 1 1 1 0 0 0 0 1 1 0 0 0 1 0 043 4.2 18.1 34.1 275.0 41.2 54.2 1 0 0 0 0 1 0 0 0 0 0 1 1 1 1 1 1 0 0 144 15.3 20.5 18.4 85.7 22.8 45.2 1 1 1 0 0 0 0 1 0 0 0 0 0 1 0 0 1 1 0 045 71.8 21.3 104.3 61.7 77.3 43.9 1 0 0 0 1 1 0 1 0 0 0 0 1 1 1 1 0 1 0 1

Novel Drug Characterization

Monogram can leverage its virus library and database to construct panels for drug characterization

Oncology Testing Services: VeraTag technology and

HERmark assay

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)

OO OH

HOOC

NHNH

S

OO

HN

O

antigen

antibody tether

fluoroscein

HERmark Assay

HERmark Assay Workflow

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

Additional VeraTag Assays

For questions about Monogram technology or assay ordering:

Andrew GaleDirector, Pharma Collaborations

agale@monogrambio.com