1 copyright 2008 genoptix, inc. mike nerenberg, md cto & sr. vp business development genoptix,...

1 Copyright 2008 Genoptix, Inc.

Mike Nerenberg, MDCTO & Sr. VP Business Development Genoptix, Inc.

B.A. University of Chicago M.D. Yale University School of Medicine UCSD Executive Program for Scientists and Engineers

Residency in internal medicine, University of Pennsylvania. Medical staff fellow, NCI 1984 - 1987 Postdoctoral fellowship, the Scripps Research Institute.

Faculty member, The Scripps Research Institute 1989 – 1996

Senior director at Nanogen 1996 – 1999

President and CTO, Molecular Reflections, Inc. 2000 – 2003

Medical director at Genoptix 2004 - 2006Vice president, business development and medical affairs

2006 - 2008


2000

Delivering Personalized And Comprehensive Diagnostic Services To Community-based Hematologists And Oncologists

And Providing Customizable BioPharma Services to Biotech And Pharmaceutical Companies.

Delivering Personalized And Comprehensive Diagnostic Services To Community-based Hematologists And Oncologists

And Providing Customizable BioPharma Services to Biotech And Pharmaceutical Companies.

Located in Carlsbad:

Approximately 100,000 total sq. ft. in two facilities,

corporate headquarters and diagnostic laboratories

(1) As ranked on the 2008 Deloitte Technology Fast 500, a ranking of the 500 fastest-growing technology, media, telecommunications and life sciences companies in North America.

Ranked as the 9th fastest-growing

technology company in North

America (1)

2008

Genoptix At-A-Glance

Founded to develop high-speed optical technologies for cellular analysis

Transformed as a specialized,

differentiated laboratory service

provider

2004 Q4 2007

GXDX IPO

Turn profitable

Q1 2007

2009 SABPA Science & Technology Forum VII

Biomarker, Pharmacogenomics and Personalized Medicine

March 21, 2009Practical Aspects of Adoption of Personalized Medicine (PM) in Oncology

Mike Nerenberg, MDCTO & Sr. VP Business Development Genoptix, Inc.


Paradigm for Personalized Therapy using Targeted Agents

Goal: the right drug to the right patient

StepsUnderstand mechanism of patient’s disease

Categorize (diagnosis)

Assign Disease Modifiers (prognosis)

Discover Therapy Modifiers (prediction)

Select targeted therapy based on above

Initiate therapy

Monitor response

Change therapy

Monitor response


This Approach has Been Around for a Long Time

Targeted therapy Circa 20 CE-

Toxins are the target


Medical Progress from Better TechnologyPersonalized Targeted Therapy Circa 1100

Target expanded

to

Bad Humors


Conversion of Practitioners to Newer Technology can be Challenging

Target:

Toxins and

Bad Humor


With Time- Better Agents and better knowledge of Mechanisms: Rapid Response to TKI in NSCLC Patients with EGFR Mutation

Hypothesis: EGFR mutation leads to modified ATP binding pocket and activates anti-apoptotic pathway.

Improved stability for binding of ATP and Gefitinib

Before After


The Foundation: Understand Mechanism of Disease in Patient

Accurate Diagnosis with Prognostic ModifiersGreatly Aided by Molecular Tests


Acute Myeloid Leukemia Approach: Circa 1980

Diagnosis Diagnostic Treatment

Pre - Leukemia Morphology Transfusion

Acute Myeloid Leukemia

Simple ChemoRx or transplant (if young)


Modern Approach to Characterization of Acute Myeloid Leukemias

AML with t(8;21)(q22;q22), RUNX1-RUNX1T1 (CBFA/ETO)

AML with inv(16)(p13q22) or t(16;16)(p13;q22), CBFB-MYH11

APL with t(15;17)(q22;q11-12), PML-RARA

AML with t(9;11)(p22;q23), MLLT3-MLL and other balanced translocations of 11q23 (MLL)

AML with t(1;22)(p13;q13), RBM15-MKL1

AML with t(9;22)(q34;q11), BCR-ABL1

AML with normal cytogenetics and cytoplasmic/mutated NPM

AML with mutation of CEBPA

AML following a myelodysplastic syndrome

AML with multilineage dysplasia

AML with MDS-related cytogenetic abnormalities

Therapy-related AML, myelodysplastic syndromes and myelodysplastic/ myeloproliferative neoplasms

AML not otherwise categorized

2008 WHO Classifications Therapies

• Highly Targeted

• Myelotarg

• Retinoic Acid Arsenic Trioxide

• Less Specific

• Etoposide

• Teniposide

• Mitoxantrone

• Idarubicin

• Carboplatin

• Adriamycin

• Ara-C

• Daunorubicin

• BM Transplant

MyeloidStem Cell

LymphoidStem Cell

Immature Basophil

Immature Eosinophil

Basophil Eosinophil Neutrophil Monocyte

N. Band

N. Metamyelocyte

N. Myelocyte

N. Promyelocyte

Myeloblast

ImmatureMonocyte

Platelets Erythrocyte

Polychromatic Erythrocyte

OrthochromaticNormoblast

PolychromaticNormoblast

BasophilicNormoblast

Pronormoblast

Lymphocyte

Megakaryocyte

MyeloidStem CellMyeloid

Stem CellLymphoidStem CellLymphoidStem Cell

Immature Basophil

Immature Basophil

Immature EosinophilImmature Eosinophil

BasophilBasophil EosinophilEosinophil NeutrophilNeutrophil MonocyteMonocyte

N. BandN. Band

N. MetamyelocyteN. Metamyelocyte

N. MyelocyteN. Myelocyte

N. PromyelocyteN. Promyelocyte

MyeloblastMyeloblast

ImmatureMonocyteImmatureMonocyte

PlateletsPlatelets ErythrocyteErythrocyte







BasophilicNormoblastBasophilicNormoblast

PronormoblastPronormoblast

LymphocyteLymphocyte

MegakaryocyteMegakaryocyte

Undifferentiated Leukemia

Undifferentiated A.L.L.

A.L.L.

B-A.L.L.

C.L.L.

M.D.S.

A.M.L.-M7A.M.L.-M5B

C.M.L./C.G.L.

A.M.L.-M3

HypereosinophilicSyndrome

A.M.L.-M1, M2, M4, M5

Undifferentiated A.M.L.

BasophilicLeukemia

Multiple Myeloma

© 2004 SFSU Instructional Technology

A.M.L. M6

Pure erythro-leukemia

T-A.L.L.

N.H.L.

M.D.S.

M.P.D.


Breast Cancer: Circa 1980

Diagnosis Diagnostic Treatment

Carcinoma in situ Excision Biopsy

Localized Morphology Mastectomy

Metastatic Mastectomy + Simple ChemoRx/Radiation


Modern Approaches to Characterization of Breast CA

Morphology

Primary

Sentinel Nodes

Immunohistochemistry

Single Markers:

ER/PR/Her2/neu

BRCA I/II status

Multigene profiles:

Risk score by multigene profile

Luminal A/B, Normal, Basal

Blood tests

Serum Markers

Circulating Tumor Cells

Highly Targeted Transtuzumab

Lapatinib

Tamoxifen

Aromatase Inhibitor

Less Specific Capecitabine

Paclitaxel/ Vinorelbine

Gemcitabine

Anthracycline

Cyclophosphamide

Radiation Rx

Mastectomy/ Oophorectomy

Diagnostics Therapeutics


Challenges to the Practicing Oncologist: Community-Based with Limited Access to Specialty Dx

85% of Oncology practice is in the Community

Small practice groups- Non-Hospital-based

Limited regional access to advanced diagnostics technology

Increasing reliance on reference labs

Communication with these labs is a key problem


Challenges to the Practicing Oncologist: Information Overload and Integration

Clinicians must select from a bewildering and constantly increasing number of diagnostic tests

By far, the single largest category of lab related error is the selection of the wrong test by the clinician

Difficult to interpret and integrate results of tests into a patient management plan

Reconcile with ever more specific therapeutic options


Integration is key

A large menu of tests is not helpful if they are selected inappropriately or misinterpreted

Our View:

Integrated Services are required for Optimal Therapy Choice & Patient Care


COMPASS

Report

Comprehensive And Integrated DiagnosisComprehensive And Integrated Diagnosis

Patient Bone Marrow Draw & Transport

Hem/Onc Customer

PCR

Cytogenetics/FISH

Flow & MorphologyGenoptix One Hempath One Patient One Diagnosis


Integrated Solutions

Partner with the oncologist to insure optimal test selection for each patient

Results should be provided with the end in mind match patient to the right therapy

100% inspection for clarity, accuracy, and comprehension


Near-term Challenges to the Lab

Variable process for State Licensures

Lack of regulatory clarity: FDA vs CLIAHome Brew

IVD MIA

ReimbursementStandard CPT Codes are relatively bad for molecular testing

State to state and company to company variation in Medicare and private insurance payment

Value Based Pricing is risky and slow

IP Barriers

Stark rules (Limit business to business relationships)


PM Requires Enhanced Role of Clinical Lab/Pathologist

Diagnosis Prognosis

Diagnosis Prognosis Treatment

Decisions Monitor

Traditional

Expanded Role

Morphology

Flow Cytometry

Karyotyping

Protein Chemistry

FISH

PCR

Gene Expression

Clinical Sequencing

FFPE Molecular Tests

Array Technology


COMPASS for blood and bone marrow

6-color Flow Cytometry

Histologic analysis

PCR

Cytogenetics

FISH

CLL Flow Cytometry Panel

Plasma Cell Labeling Index for MM

Quantitative PCR

Cytogenetics

FISH

CTC Assay

CTC Breast

CTC Colon

CTC Prostate

KRAS

EGFR

Comprehensive hematopathology assessment & review over time through CHART

Quantitative PCR for MRD

Flow Cytometry for MRD in CLL

Support Hem/Onc Customers In Many Patient Management DecisionsSupport Hem/Onc Customers In Many Patient Management Decisions

Diagnosis Prognosis Treatment

Decisions Monitor


Longer-term Challenges for Lab

Information ManagementEspecially on therapeutics (pathologists not used to this)

Limited Development resourcesRandomized prospective trials outside the range of most Commercial Labs

Prioritization of adoption

Economic


Partnering with Pharma Companies can Help

New Therapeutic Options Drive the Need for New Tests

Segments trial population and decreases risk of clinical failure Pharma

Provides insight into next generation drugs and tests Labs

Speeds up development and (hopefully) drives down cost of drug Patients

Facilitates smoother transition of new therapeutic agent/test into clinical practice Clinicians

When done in concert, everybody benefits


Benefits of Personalized Approach- Higher Quality Patient Care

More options

More rational

Less toxicity

Less futile trials

Higher quality of life for patient

In some cases longer survival


Near-term Challenges of Personalized Medicine

Nonlinear Physician AdoptionEspecially in Community

In the short term- Increased CostRequires greater specialized training for lab and clinician

Use more expensive drugs

Often requires more expensive tests


Long Term Challenges

Can personalized approaches be compatible with cost controlled medicine?

Not very compatible with fully Socialized Medicine Models

Are we in a temporary disequilibrium?

What is the true value of quality of life improvement and or extended years of survival?


How Labs Can Help in the Near-term

Set the course of therapeutics by providing a correct diagnosis

Decrease medical errors by pathologists participating in the selection and interpretation of tests

Assist with matching patients to the appropriate therapy by providing predictive tests

Accelerate availability of new therapeutics by working with Pharma

Assist with monitoring therapeutic response through molecular and cellular testing and integrated services

Thank You

1 copyright 2008 genoptix, inc. mike nerenberg, md cto & sr. vp business development genoptix,...

Documents

myelodysplastic syndrome

personalized therapy

cytoplasmicmutated npm

multilineage dysplasia

mutation of cebpa aml

bcrabl1 aml

rbm15mkl1 aml

pmlrara aml