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Paradigm A University of Michigan non-profit company to facilitate next generation clinical s equencing and clinical trials. October 24, 2012 Robert Penny M.D. Ph.D. CEO, Paradigm

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October 24, 2012

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October 24 2012

Paradigm A University of Michigan non-profit company to facilitate next generation clinical sequencing and clinical trials

October 24, 2012

Robert Penny M.D. Ph.D. CEO, Paradigm

David Mallery J.D., MBA President, Paradigm

Joe Paulauskis Ph.D. COO, Paradigm


October 24 2012

  • Mission:

  • Revolutionize the treatment and prevention of cancer and complex diseases by rigorously developing and applying post-genome science to advances in human health

  • Expression Project for Oncology

    • Building the research foundation

  • The Molecular Profiling Institute

    • Target Now

  • TCGA

    • Biospecimen acquisition, banking and management for the largest cancer research project to date

    • (65 million in NUH contracts)


October 24 2012

Paradigm

& Molecular

Profiling

Institute

Patient Care

Theranostics

Paradigm

& Molecular

Profiling

Institute

PCDx

& Target Now

TBAC

PCDx

& Target

Now

Tissue Banking

& Analysis Center

Clinical Application

PCDx

& Target Now

TBAC

Research

TGen, Harvard, Stanford, GSK, BMS, Wyeth, Research

Research

Discover

TCGA, expO, Clinical Trials

TCGA

expO,TBAC

Database

Characterization

TCGA, expO, TBAC databases

and biorepositories


October 24 2012

expO

Benefits

• New Treatments

• Diagnostic tests

• Prognostic tools

• Patents

• Publications

• Medical & Scientific

presentations

• Public release of evolving database

• New Proprietary IP

  • Genotyping

  • Haplotyping

  • Methylation Proteomics CGH

Improved clinical management

of cancer patients

Clinical Annotation Data

Expression Array Data

Public Data

Open Competition

IRB-approved Protocols

(as necessary)

TCGA

Specimen

Repository

Pharma Members

IRB-approved

Proprietary Protocols

(as necessary)


Igc s tissue network

IGC’s Tissue Network

Virginia Piper Cancer Institute, MN

Community

Hospitals of

Indianapolis, IN

St. Francis Hospital, IN

St. Vincent Hospital, IN

IGC Headquarters

Trinity, MI

St. FrancisTulsa, OK

Inova Fairfax, VA

ScottsdaleHealthCare, AZ

U of A

Tucson, AZ

Rex Hospital, NC

Texas HealthDallas, TX

Lee Memorial, FL

7 ExpO / TCGA Sites

4 TCGA Sites

Trinity MFHTyler, TX

U TN Cancer Inst., TN

3 Low Volume - Withdrew


October 24 2012

TCGA Biospecimen Core Resource Pilot Project

TCGA Biospecimen Core Resource Full Project

TCGA Tissue Source Site Network Full Project


October 24 2012

The Cancer Genome Atlas(TCGA)

Sponsored by the National Cancer Institute and the National Human Genome Research Institute, the National Institutes of Health

Human Cancer Biospecimen Core Resource

The major requirement for The Cancer Genome Atlas Pilot Project is the development of a Single, Centralized Human Cancer Biospecimen Core Resource (BCR). The BCR will oversee the acquisition of appropriately consented, standardized and rigorously collected biospecimens (patient cancer samples etc…), transport and preservation of samples and patient information to the BCR. An independent categorization and quality assurance check on these samples will occur prior to the isolation of analytes (DNA and RNA) to be distributed to the Sequencing and Characterization Centers. Samples will be de-identified with removal of patient privateinformation.

Medical Centers

Established Tissue Banks

TSS Networks IGC

Genome Sequencing Centers

Building on the technologies that were used to

complete the Human Genome Project,

high-throughput genome sequencing centers will identify the mutations in DNA associated with specific types of cancer.

Cancer Genome Characterization Centers

Several characterization technologies will be used to analyze the copy number, methylation, miRNA and expression changes associated with cancer.

Data Management, Bioinformatics and Computational Analysis

The information that is generated by The Cancer Genome Atlas network will be centrally managed and entered into public databases as it becomes available, allowing scientists to access the information during the course of this project.

Scientists will analyze the complete set of genetic and clinical data produced by The Cancer Genome Atlas network to develop a comprehensive Web-based resource which will be available to the scientific community. This resource will describe the genetic “fingerprints” of specific cancer types and will be known as The Cancer Genome Atlas. Researchers will evaluate the information contained in The Cancer Genome Atlas to determine how it can be used to speed up advances in cancer diagnosis, treatment, and prevention.


October 24 2012

Pathway Analysis in GBM

EGFR

ERBB2

PDGFRA

MET

mutation

in 7%

amplification

In 13%

amplification

in 4%

mutation, amplification

in 45%

mutation, homozygous

deletion in 17%

mutation, homozygous

deletion in 36%

NF-1

RAS

PI-3KClass I

PTEN

mutation in 2%

mutation

in 15%

AKT

amplification in 2%

RTK/RAS/PI-3Ksignaling network

86%

Proliferation

Survival

Translation

FOXO

mutation in 2%

P53signaling86%

CDKN2A

(P16/INK4A)

CDKN2B

CDKN2C

Activated oncogenes

homozygous

deletion in 51%

homozygous

deletion in 47%

homozygous

deletion in 2%

homozygousdeletion in 49%

CDKN2A

(ARF)

amplification

in 17%

amplification

in 1%

CDK4

CCND2

CDK6

amplification in 14%

MDM2

amplification

in 2%

MDM4

RB1

amplification in 6%

homozygous deletion,

mutation in 11%

TP53

RB

signaling77%

mutation, homozygous

deletion in 35%

G1/S progression

Senescence

Apoptosis


October 24 2012

Cancer’s road map is now being formed


October 24 2012

Target Now

  • Late Stage Cancer Patients

  • Profile Patients for Potential Rx Targets

  • Prospective Trial: Complete

  • DNA microarray

  • Immunohistochemistry

  • Sequencing

  • FISH

  • Other


October 24 2012

Vitamin D receptor elevated, Rx Calcitriol

  • PDGFR (Platelet derived growth factor receptor) elevated

  • Rx

  • Inhibitor molecules

  • Gleevec

  • SU112248

  • BAY43-9006


Results of the prospective trial in late stage cancer

Results of the Prospective Trial in Late Stage Cancer

  • 106 Patients

  • PFS ratio of ≥1.3

  • Deteriorating health of the patients was a significant cause of drop

  • out from the trial

  • Ratios for patient’s tumor type ≥ 1.3 PFS included:

  • colorectal 4/11 (36%), breast 8/18 (44%), ovarian 1/5 (20%), mostly

  • rare tumor types 5/32 (16%).

  • Conclusion: When using an endpoint of patient as their own control,

  • use of molecular profiling can provide clinical benefit in 26% of

  • patients who are treated according to MP results.

Diagnosis

1st recurrence

2nd recurrence

Outcome

MPbx


October 24 2012

  • CEO Robert Penny, M.D., Ph.D.

  • Founded 6 successful medical diagnostic companies

  • Secured over $65 million in NIH contracts over 5 years

  • Developed the leading revenue genomics test in Oncology today

  • Built one of the first clinically annotated gene expression databases

  • Leadership role The Cancer Genome Atlas project

  • Venture capital and medical diagnostic company

  • Experienced scientist

  • Co-founded 3 biotech companies

  • Leadership TCGA

  • Pfizer Global Head of Pharmacogenomics

  • Leadership TCGA

President David Mallery, J.D., M.B.A.

COO Joe Paulauskis, Ph.D.


October 24 2012

Specimen analysis, coupled with pathology expertise, state-of-the-art bioinformatics interpretation and personalized customer service that:

  • Benefits patients by providing the most advanced information available for cancer treatment

  • Benefits clinicians by providing accurate, validated diagnostic, prognostic and therapeutic information

  • Benefits UMHS by

    • establishing UMHS as a national leader in personalized medicine

    • attracting additional patients

    • enhancing UMHS ability to conduct clinical trials

    • creating a new revenue source for UMHS


October 24 2012

Pathologist & Oncologist Reviewed

Tumor Biopsy

(FFPE)

Informed Consent

Patient Delivery

Sequencing

  • Clinical Trial Eligible

  • Actionable Results

Analysis

3–4 Day Turnaround

Laser

Cryo

Enrichment

&

Or

oncologist

ordered


October 24 2012

Millions of papers interrogated

Bench

Tens of thousands of articles identified

Test ID and development

Thousands of articles evaluated

Division of dedicated professional staff

Real-time evidence report with weekly updates

Thousands of articles reviewed

and graded

Bedside

Thousands of rules developed

Hundreds of articles cited


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