The Killer in Context: A Pathologist's Perspective on Companion Diagnostics
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Transcript of The Killer in Context: A Pathologist's Perspective on Companion Diagnostics
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Confidential and proprietary to Ventana Medical Systems, Inc. For internal use only. Do not copy. Do not distribute.
The Killer in Context: A Pathologist's Perspective on Companion Diagnostics Mary T. Padilla, M.D., Medical Director Ventana Companion Diagnostics
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Market Conditions Pharma’s & Dia’s need create ideal CDx environment
Targeted Therapy &
Patient Selection
Differentiated Assays &
Medical Value CDx
• Rising costs vs. lowering program success
• Regulators mandate improved clinical outcomes
• Payors mandate better health economics
• Increasing macro economic pressures drive decreasing reimbursement
• Low cost competitors drive pricing pressure
• Maturing business (decline in capital, automation saturation)
Rx - Challenges Dx - Challenges
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Prototype Assay Development and CAP/CLIA studies
Ventana Companion Diagnostics Solution
Prototype Assay
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AGENDA
Current Case for Tissue
Immunotherapy
Future NGS
Q&A
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Tissue context is required for diagnosis, IHC can not be displaced by molecular methods
A DNA test would produce identical results at all three stages
Larvae
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Cocoon Butterfly
PD-L1 Staining
Tumor -
Rx Effective Rx Effective No Rx Benefit Infiltrate +
Tumor +
Infiltrate +
Tumor +
Infiltrate -
Information embedded in the tissue
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6 Intact Extracted
Chemistry in Context
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Medical Needs The Patient The Lab/The MD What do I have? Diagnosis
What caused it? Etiology: Infections/Genetic
What explains my symptoms? Pathogenesis
What are my prospects? Prognosis
Has it spread? Metastasis
What is my treatment? Therapeutic Targets
Will I be cured? Response Prediction
Will I be hurt? Toxicity Prediction
How will I be followed? Monitoring
Will it return? Relapse
Will others in my family get it? Predisposition Screening
How will you communicate the results? Medical Report
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Objectives
Demonstrate how slide-based tissue chemistry innovations will change cancer care
Method
– Describe where we are today – Describe our unsolved problems – Describe innovative solutions
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The Challenges
– Deliver more results relevant to patient prognosis and therapy.
– Deliver more molecular-based assays.
– Deliver more automated, standardized results.
– Communicate results better.
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The Key Scientific Advances
Beyond diagnosis to therapeutics
Beyond single analyte to multiplexing
Beyond protein to gene plus protein assays
Beyond qualitative to quantitative assays
Beyond informatics to cellular informatics
Beyond written reports to patient-centric reports
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Utility of Slide-Based Tissue Chemistry Simultaneous analysis of morphology, gene and protein status
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Morphology Gene status Protein status
H&E: Hematoxylin&Eosin (Dye)
ISH: in situ Hybridization) (DNA/RNA Probe)
IHC: Immunohistochemistry
(Antibody)
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H&E IHC
Normal Tissue
Carcinoma
The Importance of Tissue Analysis in Morphologic Context Patient 1: 48 year old female with 2 cm invasive ductal breast carcinoma (H&E).
Estrogen Receptor
on normal
cells
Conflicting test results for Estrogen Receptor (IHC ER-neg/PCR ER-pos)
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The Importance of Chemistry in Morphologic Context Breast Cancer: Heterogeneity of HER2 Expression
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Objective 4x
3+
2+ 1+
0 Predicts Therapy Failure
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Patient 2: female with breast carcinoma and recurrent tumor despite anti hormone therapy.
IHC: HER2-positive Ki67 H&E IHC: ER-positive
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The Importance of Tissue Analysis in Morphologic Context
Applying tests on various biomarkers helps explaining recurrence of HER2 positive tumor and allows appropriate therapy guidance.
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Utility of Tissue-Based Chemistry
– Reveals functional morphology.
– Reveals microenvironment.
– Reveals driver events.
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IHC Uncovers Heterogeneity and Reveals Functional Morphology Hematoxylin and Eosin Estrogen Receptor Progesterone Receptor
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“ Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing”
Gerlinger et al, NEJM 366:883-92, 2012
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The Key Observations
In tumor heterogeneity there is genetic divergence with consequent phenotypic convergence which alters cell function at the protein level which undergoes Darwinian selection and evolutionary adaptation and probable therapy failure.
Gerlinger et al, NEJM
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Nagle, et al The Prostate 9999:1-7 (2013)
Loss of PTEN Expression in Prostate Cancer
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Coussens et al. Science 339, 286 (2013)
Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?
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AGENDA
Current Case for Tissue
Immunotherapy
Future NGS
Q&A
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Immune Cell Modulators – A Class on its Own A number of these receptors can be analyzed by IHC
B7-H3
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PD-1/PD-L1: A Critical Immuno Checkpoint Pathway
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PD-1/PD-L1: A Critical Immuno Checkpoint Pathway
anti-PD-1; NSCLC 40x anti-PD-L1 (SP); NSCLC 40x
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Surface Markers: Critical for Immune Cell Classification
anti-CD3 (SP7); anti-CD16 (SP96) NSCLC 40x
anti-CD3 (SP6) NSCLC 40x
anti-CD8 (SP16) NSCLC 40x
anti-CD3 (SP6) anti-CD8 (SP16) NSCLC 40x
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Role of IDO1in Regulating Anti-Tumoral Immunity
anti-IDO1 (SP); NSCLC 10x
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Other Immune Modulating Markers: B7H3
anti-B7-H3 (SP206); NSCLC 40x
Zang X , and Allison J P Clin Cancer Res 2007;13:5271-5279
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Immunohistochemistry illustrates key interactions – Summary points for IHC/ISH
– Morphology
– Interactions
– Tumor vs. Infiltrate (or “inflamate”)
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“We are leaving the world of commoditized diagnostic, what is it,
and going to higher value tests linked to therapy, what to do.”
Dr. Tom Grogan, Founder Ventana Medical Systems, Inc.
Where we are going …
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AGENDA
Current case for Tissue
Immunotherapy
Future NGS
Q&A
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Cancer Treatment in the Future?
A. Bacall, The New Yorker
"Here's my sequence”
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Next Generation Cell Signaling Assays PI3k
Measuring Activation Status
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– Personalized medicine utilizing the best available technologies
– Clinically relevant information
– Broad patient access
Future of NGS
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AGENDA
Current Case for Tissue
Immunotherapy
Future NGS
Q&A
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Question and Answer Session From in the room and beyond
- Your questions first
- Live Tweet format for additional questions
- Follow us @ventana
- Review tweets from the conference at @worldcdx
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Thank you.
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VENTANA Empowering | Personalized Healthcare www.roche.com www.ventana.com
© 2014 Ventana Medical Systems, Inc.
VENTANA and the VENTANA logo are trademarks of Roche. All other trademarks are the property of their respective owners. Ad-pro # here E5248A-5
Doing now what patients need next
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VENTANA Empowering | Personalized Healthcare www.roche.com www.ventana.com
© 2014 Ventana Medical Systems, Inc.
VENTANA and the VENTANA logo are trademarks of Roche. All other trademarks are the property of their respective owners. Ad-pro # here E5248A-5
Doing now what patients need next