IGC PPT PRESENTATION.PPT

Molecular Testing in the Age of Precision Medicine
Confidential

Historical Highlights
Cancer
• Second leading cause of death in the world
• Nixon’s “War on Cancer” & the search for the magic bullet
• Time for a Change in Strategy
• Leverage the completion of the Genome Project to
characterize cancer through genomics – IGC’s expO
• Use expO’s success to convince the NCI that a bigger project
would be feasible – The Cancer Genome Project
• Characterize patients for Rx based on molecular pathways and
associated therapies – IGC’s MPI test Target Now (Caris Life
Sciences)
• Build the evidence for pathways medicine (targeted) through
a prospective clinical trial

IGC and Affiliate Company History
BCR & TSS
Pilot Project BCR
J. Clin. Onc.
Tissue Banking
And Analysis Center
Acquisition
1999 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Confidential

Total IGC and Affiliate Headcount
Total IGC and Affiliate Headcount
450
411
400 395
350 344
300
Headcount 282
250
Cumulative
200
150
134
111
100
50
-
2008 2009 2010 2011 2012 2013
4

expO
Public Data
Benefits Benefits
Open Competition
IRB-approved Protocols
(as necessary)
Improved clinical management
Genotyping Genotyping
of cancer patients
Haplotyping Haplotyping • New Treatments
Clinical Clinical
Annotation Annotation Data Data • Diagnostic tests
Specimen TCGA
Repository Methylation Methylation • Prognostic tools
Expression Expression • Patents
Array Array Data Data
Proteomics Proteomics • Publications
• Medical & Scientific
presentations
CGH CGH
• Public release of evolving
Pharma Members
database
IRB-approved
• New Proprietary IP
Proprietary Protocols
(as necessary)


TCGA Components

Cancer’s road map is now formed

Cancer Patients
Profile Patients for Potential Rx Targets
• Prospective Trial:
Complete
• DNA microarray
• Immunohistochemistry
• Sequencing
• FISH
• Other

Results of our Prospective Clinical Trial in Late Stage
Cancer
(JCO Nov. 2010)
• 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
biopsy

3–5 Day Turnaround
Pathologist &
Informed Tumor Biopsy Oncologist
Consent (FFPE) Laser Reviewed Patient
Capture Delivery
Enrichment
&
Sequencing
Or
oncologist 1) Clinical Trial
ordered Eligible
Analysis 2) Actionable
Results
Confidential

PCDx Report Delivered
Confidential

Patient example #1
63 year old woman with adenoid cystic carcinoma
of the breast:
- extensive lung metastases (now symptomatic)
- prior therapy with
• 5FU
• vincristine
• cytoxan
• methotrexate
• thalidomide
• phase I farnesyl transferase inhibitor
Confidential

Continued
Patient was being operated on at one of the nations large
cancer centers.
• debulk lung metastases and decorticate to
improve pulmonary function for the patient.
The physician in charge said by the way: “The patient doesn’t
want any chemotherapy so you need to find something else
that has a chance of helping her”
Confidential

Continued
Confidential

Continued
Ratio T/Ref Gene Name Description
Thioredoxin interacting protein (vitamin D-3 upregulated protein-1), a negative
6.862 TXNIP regulator of thioredoxin that is induced by the stress response and may play a
role in the redox regulation of differentiation, may have an anti-tumor effect
Protein containing 11 leucine rich repeats, and a leucine rich repeat N-terminal
6.857 I_1002429
cysteine rich domain, has weak similarity to thyroid stimulating hormone receptor
(human TSHR), which is a G protein-coupled receptor that regulates thyroid cells
Ephrin type B receptor 4, a member of the Eph-related subfamily of receptor
6.848 EPHB4 tyrosine kinases, preferentially enhances megakaryocytic and erythrocytic
differentiation of progenitor cells; expression is elevated in colon carcinoma
Calmodulin-like skin protein, a member of the calmodulin family of calcium-
6.826 CLSP binding proteins, may play a role in keratinocyte differentiation, shows altered
expression in sun-damaged skin
Retired, was Protein with high similarity to immunoglobulin lambda (mouse
6.767 I_965438 1810027O01Rik), which associates with heavy chains to form antibodies
(immunoglobulins), contains two immunoglobulin (Ig) domains
NM_00342 Homo sapiens zinc finger protein 45 (a Kruppel-associated box (KRAB) domain
6.717
5.1 polypeptide) (ZNF45), mRNA
Lipase member H, phospholipase that may be involved in lipid metabolism, a
6.648 LIPH member of the triglyceride lipase family, contains an amino-terminal lipase
domain and a carboxy-terminal domain
Protein containing a Chromo domain, which bind chromatin, has moderate
similarity to a region of chromobox homolog 4 Drosophila Pc class (human CBX4),
6.600 CBX7
which is a component of the HPC-HPH Polycomb group complex and functions as
a transcriptional repressor
Protein with low similarity to S. cerevisiae Cwh43p, which is involved in
6.567 FLJ21511 Vitamin maintenance D receptor of cell wall integrity elevated, Rx Calcitriol
Confidential

Continued
• Was doing well on vitamin D, unfortunately she
then had increasing disease and bone mets with
bone pain along with a very bothersome cough.
Confidential

Continued
Second Target Noted on Microarray
Other target present was
•PDGFR (Platelet derived
growth factor receptor)
•Inhibitor molecules
ØGleevec
ØSU112248
ØBAY43-9006
Microarray to look for possible
targets.
Patient begun on Gleevec - bone pain
disappeared, lesions gone! Looked and felt great!
Confidential

Continued
• Patient feeling worse again, pain returned
• Dan was going to change therapy
• But she had stopped the Gleevec because she
couldn’t afford it!
• Back on Gleevec now- feels great- cough and bone
pain gone!
• She remained in complete remission for another
1.5 years
Confidential

Patient example #2
Dr. Larry Einhorn (Indiana University)
Dr. Einhorn is widely recognized for developing in 1974 a
chemotherapy regimen for testicular cancer that revolutionized
the cure rate from 5% to 95%
A New Patient JL
24 year old male with a testicular cancer – yolk sac tumor
- Unsuccessful prior therapy with
• Bleomycin
• Cisplatin
• Etoposide
• Carboplatin
Confidential

Analyzed with Paradigm’s Next Generation Sequencing Panel
> Elevated Her 2 & 3 Target by mRNA and Copy Number
> Confirmation by standard Breast Cancer FISH analysis
> Patient started on Herceptin and Perjeta therapy 2 weeks ago
> Waiting for follow up information
> Six patients sent from Dr. Einhorn, 4 patients had drugable
targets.
> Awaiting clinical outcomes
Confidential

IGC: 3-Year Strategy
• 2011: Develop a plan for transition away from NIH
contracts. BCR ending 2012, TSS ending 2013
Ø Create a spinoff medical diagnostic company
Ø Create a spinoff national biomarker company
Ø Prepare to transition IGC from reliance on Federal
contract dollars to new revenue sources
Confidential

IGC: 3-Year Strategy & the future
• 2012:
Ø Create and launched the diagnostic company: Paradigm
Ø Continued work on ABA now NBDA with founders:
• C-Path, IGC, ASU
Ø Transitioned away from NCI contracts while preserving
the last year of the TSS contract
• 2013:
Ø Successfully built the spin off diagnostic company:
Paradigm, in Ann Arbor and Phoenix
Ø Introduced a comprehensive genomic cancer test
Ø Hired 30 FTE’s between Phoenix and Ann Arbor
Ø Met milestones in advance for year 1
Ø Assisted in the success of NBDA
• 2014:
Ø Explore a partnership between IGC’s spin off company Paradigm and
the University of Arizona
Ø Underway
Ø Establish market share in Diagnostics with Paradigm’s Cancer Diagnostic
Ø Assist in the success of NBDA
Ø IGC to explore yet another new company!
Confidential

Thank You