Abbott Molecular (formerly Vysis) and CLL

John Proffitt September 21, 2006

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Abbott Molecular and CLL

Brief Overview of Abbott Molecular

Current CLL Related Products

CLL Related Products in Development

Other Abbott CLL Activities

What are CRC Study Needs?

Abbott Molecular Overview

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Abbott

Abbott Molecular

Vysis Celera

Our Foundation

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Des Plaines, Illinois

140 Million in Sales140 Million in Sales 500 Employees500 Employees Dedicated Molecular FacilityDedicated Molecular Facility

ResearchResearch

Quality Quality

ManufacturingManufacturing

Molecular Sales, Service Molecular Sales, Service and Support and Support

New Molecular Facility

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Infectious Disease

TransplantationConstitutional

Genetic Testing

Innovation

Through

Automation

Genomics

Discovery

Abbott Molecular FocusUnmet Medical Needs

Oncology

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ASR

HBV**

HCV Quant**

HCVGenotype**

HSV1,2*

CMV**

EBV**

Enterovirus*

Parvovirus**

VZV**

Infectious Disease

IVD

HIV-1

HCV

CT/NG

* Future Launches** Analyte Specific Reagent

IVD ViroSeq

RealTime PCR

Sequencing

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Current CLL Related Probes

Mixes

• P53 orange/ATM green (can add aqua MYB)

• D13S319 orange/LSI 9q34(LAMP1)aqua/CEP12 green

• IGH/CCND1 XT (mantle cell lymphoma)

Individual Probes

• P53 orange

• ATM orange

• MYB aqua

• D13S319 orange

• LSI 9q34(LAMP1) green

• CEP12 orange & green

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Deletions & Trisomy in CLL Compare SS LOCI w/ Vysis

CLL

• Most common adult leukemia

• Highly variable clinical course

• Detection by cytogenetics unsatisfactory

• Emerging variety of therapeutic options

Dohner, H, et al. NEJM, Vol. 343, No. 26, 2000Dohner, H, et al. NEJM, Vol. 343, No. 26, 2000

11q22deletion11q22deletion

p53 deletionp53 deletion

+12q13 +12q13

13q14 deletion13q14 deletion

P53>11q>12q>13q

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Normal

ATM Deletion p53 Deletion

CLL

Normal 2O2G

Abnormal 2O1G Abnormal 1O2G

Two probe mixture p53/ATM

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Trisomy 12

Three probe Mixture: D13S319(q14), LAMP1, CEP12

Trisomy 12 & del(13q14)

CLL

Normal 2O2G2A Abnormal 2O3G2A

Abnormal 1O3G2A

Normal

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Mayo Probe Set Requested by G. Dewald for CRC

P53 orange/CEP17 green

ATM orange/ CEP11 green

D13S319 orange/ LAMP1(LSI 9q34) green

MDM2 orange/ CEP12 green

MYB orange/ CEP6 green

CCND1 orange/IGH green XT

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Mayo & Vysis Set Comparison & Question

•P53/ATM/MYB(optional)

•D13S319/LAMP1/CEP12

•IGH/CCND1 XT

P53/CEP17

ATM/ CEP11

D13S319/ LAMP1

MDM2/ CEP12

MYB/ CEP6

CCND1/IGH XT•3 hybs vs. 6 hybs•7-8 vs. 12 probes•What data supports 12 probe mix superiority?•Will CRC study generate the needed data?•Is 6q marker needed?•Is MYB 6q23 superior to 6q21/other?•MDM2(12q15) vs. 12q13(CHOP,CDK4,GLI) orCEP12?•ATM vs. FDX/RDX?

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Mayo Set; Current Status at Vysis

P53/CEP17: Ready for External Testing; Sale~ 1/18

ATM/CEP11: Assay Optimization; Sale~ 2/5

D13S319/LAMP1: Assay Optimization; Sale ~1/18

MDM2/CEP12: External Testing, CLL & Liposarcoma, Sale~11/23

MYB/CEP6: Bulk Probes Made, Market, CRC?

CCND1/IGH XT: Existing Product

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Other Abbott CLL Activities

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Targeting the unmet medical need: the Abbott Laboratories oncology approach.Clin Adv Hematol Oncol. 2005 Sep;3(9):703-10.

Endothelin A-receptor antagonist atrasentan/Xinlay

Angiogenesis inhibitors ABT 510, a thrombospondin mimetic:

ABT 869, a multitargeted receptor tyrosine kinase inhibitor

ABT 828, recombinant human plasminogen kringle 5

Cell proliferation inhibitor/antimitotic agent ABT 751

Multitargeted receptor tyrosine kinase inhibitor ABT 869

Apoptosis inducer/Bcl-2 family inhibitor ABT 737

Monotherapy efficacy in xenograft models of small-cell lung cancer and lymphoma. Affinity for bcl-2, Bcl-XL & Bcl-w 100-1000x greater than other other cmpds. Nature. 2005 Jun 2;435(7042):677-81

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DNA Methylation Assay

Novel Method from Rubicon Genomics

Involves PCR and WGA (Whole Genome Amplification)

WMA (Whole Methylome Amplification)

Not Currently Focused on CLL

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CGH Microarray Technologies

Next Generation Fully Automated

System

Automation

*

*For Research Use Only **In Development

**

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Automation Choices

SpecimenReceived

ThermoBrite

SlidePre-treatment

& Washing

VP2000

Denaturation &

Hybridization

Slide Scanning& Enumeration

AutoVysion

ThermoBrite

New!

Xmatrx*

Pre-treatment, Washing,

Denaturation,Hybridization &Final Coverslip

*In Development

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What Are CRC Study Plans & Probe Needs?

What are the studies/what goals?

What probes?

Are loci fixed or do some need investigation?

When are the probes needed?

What quantities of probes?

How to distribute?

Is a single entity able to bind all institutions in an agreement?

•Like to avoid multiple agreements w/ multiple sites.