Transcript Strategic Assessment of the UMHS Clinical Research

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.
David Mallery J.D., MBA
Joe Paulauskis Ph.D.
CEO, Paradigm
President, Paradigm
COO, Paradigm
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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)
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Paradigm
& Molecular
Profiling
Patient Care
Institute
Theranostics
Paradigm
& Molecular
Profiling
Institute
Tissue Banking
& Analysis Center
TBAC
PCDx
& Target
Now
PCDx
PCDx
& Target Now
& Target
Now
Clinical Application
TBAC
Research
TGen, Harvard, Stanford, GSK,
BMS, Wyeth, Research
Research
Discover
TCGA
expO,TBAC Characterization
Database
TCGA, expO, Clinical Trials
TCGA, expO, TBAC
databases
and biorepositories
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expO
Public Data
Open Competition
Benefits
IRB-approved Protocols
(as necessary)
Improved clinical management
of cancer patients
Genotyping
Specimen
Repository
Clinical
Annotation Data
• New Treatments
Haplotyping
• Diagnostic tests
TCGA
• Prognostic tools
Methylation
Expression
Array Data
• Patents
• Publications
Proteomics
CGH
Pharma Members
IRB-approved
Proprietary Protocols
(as necessary)
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• Medical & Scientific
presentations
• Public release of evolving
database
• New Proprietary IP
IGC’s Tissue Network
Virginia Piper Cancer
Institute, MN
Community
St. Vincent Hospitals of
Hospital, IN Indianapolis, IN
IGC Headquarters
St. Francis
Tulsa, OK
St. Francis
Hospital, IN
Trinity, MI
Inova Fairfax, VA
Scottsdale
HealthCare, AZ
U of A
Tucson, AZ
7 ExpO / TCGA Sites
Rex Hospital, NC
Texas Health
Dallas, TX
Lee Memorial, FL
4 TCGA Sites
Trinity MFH
Tyler, TX
3 Low Volume - Withdrew
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U TN Cancer Inst., TN
TCGA Biospecimen Core Resource Pilot Project
TCGA Biospecimen Core Resource Full Project
TCGA Tissue Source Site Network Full Project
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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
Established Tissue Banks
TSS Networks IGC
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 private information.
Genome Sequencing Centers
Medical Centers
Cancer Genome
Characterization 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.
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.
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Pathway Analysis in GBM
EGFR
ERBB2
mutation, amplification mutation
in 7%
in 45%
mutation, homozygous
deletion in 17%
NF-1
PDGFRA
MET
amplification
In 13%
amplification
in 4%
PI-3K
RAS
mutation in 2%
Proliferation
Survival
Translation
86%
CDKN2A
(ARF)
amplification in
14%
CDKN2B
CDKN2C
homozygous
deletion in 47%
homozygous
deletion in 2%
(P16/INK4A)
homozygous
deletion in 51%
amplification
in 17%
MDM2
CDK4
CCND2
CDK6
amplification
in 2%
MDM4
amplificatio
n
in 1%
RB1
amplification in 6%
homozygous
deletion,
mutation in 11%
TP53
Senescence
mutation in 2%
CDKN2A
homozygous
deletion in 49%
mutation,
homozygous
deletion in 35%
amplification in 2%
FOXO
Activated oncogenes
86%
mutation, homozygous
deletion in 36%
mutation
in 15%
AKT
RTK/RAS/PI-3K
signaling network
P53
signaling
PTEN
Class I
G1/S progression
Apoptosis
RB
signaling
77%
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Cancer’s road map is now being formed
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Target Now
Late Stage Cancer Patients
Profile Patients for Potential Rx Targets
• Prospective Trial: Complete
• DNA microarray
• Immunohistochemistry
• Sequencing
• FISH
• Other
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Vitamin D receptor elevated, Rx
Calcitriol
PDGFR (Platelet derived growth factor receptor)
elevated
Rx
Inhibitor molecules
Gleevec
SU112248
BAY43-9006
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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
2nd recurrence
1st recurrence
MP bx
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Outcome
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
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President
Venture capital and
medical diagnostic
company
Experienced
scientist
Co-founded 3
biotech companies
Leadership TCGA
David Mallery, J.D., M.B.A.
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COO
Pfizer Global Head of
Pharmacogenomics
Leadership TCGA
Joe Paulauskis, Ph.D.
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
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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
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Academic
Institutions
Physician
Networks
Cooperative
Groups
Life Sciences
Companies
Patient
Advocacy
Groups
Reference
Laboratories
Pharmaceutical
Companies
CRO’s
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3–4 Day Turnaround
Informed
Consent
Pathologist &
Oncologist
Reviewed
Tumor Biopsy
(FFPE)
Laser
Cryo
Enrichment
&
Sequencing
Or
oncologist
ordered
Analysis
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1) Clinical Trial
Eligible
2) Actionable
Results
Patient
Delivery
Millions of papers
interrogated
Tens of thousands of
articles identified
Thousands of articles evaluated
Division of dedicated
professional staff
Real-time evidence
report with weekly
updates
Thousands of articles reviewed
and graded
Thousands of rules developed
Hundreds of articles cited
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Services
Clients
Diagnostic Panels:
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~500 targets/cancer pathways providing
the associated therapies and supporting
evidence
Additional proprietary panels + analysis
based on targeted sequencing for clinical
trials, actionable Rx, R & D
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UMHS Clinical Systems
Physicians and oncology groups
Patients/Advocacy Groups
Pharma/industry
Payors
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Pharma-sponsored clinical trials
Clinical research organizations
Advocacy Groups
Payors
Academic Investigators
Industry Services:
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Biobanking support & consulting
Standard protocol development
Clinical trial design and planning
Companion molecular diagnostics
Sequencing, IHC, FISH, SNP, Tissue
Microarray, Laser Cryo Enrichment
Payor consulting and contracting
Clinical evidence database
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