Download The Belfer Institute For Applied Cancer Science is a Bridge Between

Dana-Farber Cancer Institute
Capabilities and Collaboration Opportunities
Japan Delegation Visit October 22, 2014
O. Prem Das, PhD
Chief Research Business Development Officer
http://pinker.wjh.harvard.edu/photos/boston_I/pages/Weeks%20bridge.htm
The Belfer Institute For
Applied Cancer Science is
a Bridge Between
Academia & Industry
© 2012 – Belfer Institute for Applied Cancer Science
DFCI’s Distinguishing Feature: The “Balanced Portfolio”
• A 50:50 mix of outstanding patient care and
cutting-edge research
• Part of our core mission
The Balanced Portfolio drives the way we
think about cancer research
DFCI: Balanced Portfolio
A 50:50 mix of outstanding patient care and cutting-edge research
Key differentiating factor: next highest institution has a 4:1 ratio
$500M
Expenses
$500M
Expenses
Clinical
Margin
Philanthropy
Clinical
Margin
Clinical
Revenue
Clinical
Activity
Research
Revenue
Research
Activity
Academic Structure
• All Dana-Farber faculty are also faculty in departments at one
of the Harvard schools (mostly HMS, some HSPH)
• IP and Research belongs to where the laboratory is located
• Dana-Farber has 7 internal departments
– Medical Oncology
– Pediatric Oncology
– Radiation Oncology
– Psychosocial Oncology and Palliative Care
– Cancer Biology
– Cancer Immunology and AIDS
– Biostatistics and Computational Biology
Clinical Care & Research
• Pediatric oncology care delivered through Jimmy Fund Clinic & divisions in
Boston Childrens Hospital
– Organized in programs & disease centers
•
Medical oncology care delivered through 12 Disease Centers
– Anatomically based Disease Centers
– Early Drug Development Center
• Disease Centers are sites of clinical trial activity
•
Clinical trials managed through Dana-Farber/Harvard Cancer Center
(DF/HCC)
– Consortium of 5 hospitals (DFCI, BIDMC, BWH, BCH, MGH) and 2
Harvard schools (HMS, HSPH)
– Single IRB oversees trials at all 5 hospitals
– DF/HCC runs over 700 active trials enrolling over 3500 patients
Research Model
•
Faculty laboratory & group leaders are “independent contractors”
– DFCI provides support for unfettered discovery research
– Recruitment focused on “best athlete
•
Amended model needed
– Pace of translation of research findings to clinical impact too slow
– DFCI recognized need to introduce concepts of project management
into academic translational research
•
DFCI Strategic Planning
– Goal: implement project management principles to translate
discoveries into clinical benefit while preserving the culture of
independent discovery
– Faculty identified 10-12 areas ripe for translation
– Created “Integrative Research Centers” around each
The “new” Research Infrastructure at DFCI
INTEGRATIVE RESEARCH CENTERS
DISEASE CENTERS
• Bone and Sarcoma
• Cancer Genetics
• Cutaneous and Mohs Surgery
• Gastrointestinal
• Women’s Cancers
• Head and Neck
• Genitourinary
• Thoracic
• Hematology
• Neuro
• Experimental therapeutics
• Psychosocial
SELECTED TECHNOLOGIES
• NextGen DNA sequencing
• PDX Models
• Pathology
• Proteomics
• Chemistry
• Computational Biology
• Imaging (animal and human)
• Belfer Institute for Applied Cancer Science
• Cancer Vaccine Center (CVC)
• Blais Proteomics Center
• Cell Manipulation Core Facility (CMCF)
• Center for Biomedical Imaging in Oncology (CBIO)
• Lurie Family Imaging Center (LFIC)
• Center for Cancer Computational Biology (CCCB)
• Center for Cancer Genome Discovery (CCGD)
• Center for Cancer Systems Biology (CCSB)
• Center for Clinical and Translational Research
• Center for Functional Cancer Epigenetics (CFCE)
• Center for Molecular Oncologic Pathology (CMOP)
• Joint Center for Cancer Precision Medicine
• Medicinal Chemistry Core
• Early Drug Development Center (EDDC)
INVESTIGATORS
• Basic
• Translational
• Clinical
Integrative Research Centers
•
Founded on business rules & accountability
– Faculty leader of each Center charged with developing a business plan
– Business plan included explicit milestones & deliverables over 5 years
• Deliverables built around specific project endpoints rather than academic
metrics
– Financial plan required to bring Center to self-sufficiency within 5 years
•
Incentivizing “independent contractor” faculty to lead Centers
– Seed funding to start Center activities
• Not released until business plan approved by President
– Research scientist hiring track
• Non-tenure track faculty with project management experience
• Rigorous promotion ladder & opportunities for responsibility & advancement
• Over 100 research scientist faculty members
•
Oversight
– VP for Strategic Planning & CSO for day-to-day
– Internal Oversight Committees & External Advisory Boards
The Lurie Family Imaging Center:
State of the Art Experimental Therapeutics Facility
The Lurie Family Imaging Center
MRI
Harbor Campus
Opened August 2009
14,000 sq ft
3,300 cages
Optical
Full treatment options:
•Expert technical support
•Radiotherapy
Full spectrum of endpoints:
•Anatomic and molecular imaging
•Conventional metrics
•Access to mouse histopathology
Ultrasound
PET/
SPECT/CT
Radiochemistry
Full spectrum of mouse cancer models:
•GEMM
•Primary xenografts
•Cell line xenografts
Image-guided
irradiator
Expert design and data analysis:
•Physicists
•Cancer Biologists
•Biostatistician
•Clinicians
•Data/Image Analysts
Belfer Institute’s Scientific Scope
•
Target discovery
–
•
Target validation
–
–
–
–
•
Tumor maintenance in vivo
Delineate therapeutic significance of new target
Responder ID: the context
Define clinical path
Target biology to enable
drug discovery & development
–
–
–
–
•
Both genomic evidence and biological (in vivo) activities
Mechanisms: response, resistance, combination
Target engagement and predictive biomarkers
Delineate mechanisms of resistance
Develop clinical strategies to address resistance
Developing strategies for existing therapies
– Identify & develop best combination therapies
– Expand indications
Target Validation
Deep Target Biology
Clinical Path Hypothesis
Address clinical path
hypotheses upfront
Patient Derived Xenograft (PDX) disease models
• PDX mouse models recapitulate the genetic complexity
of human cancers
• Established by implanting mice with patient cancer
cells/tissues from biopsy samples
• Solid and liquid tumor PDX models to help develop new
therapies, combinations, and biomarkers
• Luciferized PDX models created for real-time
tumor monitoring
• Tumor volume can be correlated with serum
biomarker expression or circulating free human
DNA (cfDNA)
• Valuable for drug efficacy and drug combination
studies
PROFILE: Institution-wide Genomic Profiling of Tumors
•
DFCI sees 16,000 new patients per year
•
Management and integration of 2 categories
of data
– Clinical data: Data generated during the
course of clinical care of patients
– Specimen data: molecular or other data
derived from specimens
• PROFILE: Institution-wide Genomic Profiling
of Tumors
– offers specimen genotyping & clinical
data linkage for all patients
– 75% patient consent rate
•
Process for working with companies
PROFILE’s Impact
•
Clinical Impact
–
–
–
•
Research Impact – Genotype/Phenotype Studies in Humans
–
–
–
•
Clinically actionable results returned when participants consent to return of results
Allows physicians to identify patients whose tumors have mutations for which approved
drugs are available
Allows physicians to identify patients who may qualify for clinical trials requiring specific
mutations for eligibility
Can ask questions about the association of specific mutations with clinical behavior
Eg, is a specific set of mutations associated with Herceptin failure in Stage II breast
cancer patients?
Eg, does the presence of a specific mutation predict for a specific clinical behavior?
Research Impact – Clinical Research
–
Investigators can retrieve all patients with a specific mutation & contact those who have
consented to re-contact for enrollment on a trial of an agent directed against that
mutation
Office of Research and Technology Ventures (ORTV)
Four areas of activity:
•
Patent inventions to
incentivize industry licensing
•
License patents to companies
big and small
• Generate industry-sponsored
research and collaborations
•
Serve research community:
MTAs, CDAs etc.
Our mission: Get DFCI technologies into the clinic
What has changed in Oncology Drug
Development?
Drug Candidates
from Research
FDA-approved
Cancer Drug
<10% Overall Success
VALUE
RISK
Target
Discovery
Target
Validation
Academia
Small
Molecule
Antibody/
Biological
Animal
PoC
Optimize
lead
Pre-IND
Tox PK/PD
Industry, but Academia?
Venture capital investment in biotech lower
No funding to reduce early stage risk
15
Phase I,
II Trials
Phase
III Trials
FDA
Approval
Industry
Cancer driven by mutations, not tissue type
Clinical development model unclear
Activity Growth
80
70
Inventions
60
Patent Filings
50
40
30
Growth would be significant
even if new disclosures were flat
20
10
0
2008 2008 2009 2009 2010 2010 2011 2011 2012 2012 2013 2013 2014 2014
H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2
16
$30
TOTAL SRA FUNDING
$25
TOTAL LICENSING INCOME
$20
$15
$10
$5
2014
2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
$-
2001
Millions
Income Trends and Goals
Small Molecules in the Clinic: Productivity
License Date Development Stage
10/7/2008
Phase I in 2012
2/11/2010
Phase I in 2013
2/19/2010
Phase I in 2013
2/11/2010
Phase I in 2014
12/19/2011
Phase I in 2012
7/22/2011
Phase I in 2013
12/9/2011
Preclinical (nonchemistry)
4/9/2013
Preclinical
4/9/2013
Preclinical
Start-up Success
Most DFCI start-ups are successful in exits and raising money
2007
2008
2009
Eutropics
(NIH-funded)
Immunology
Company
(nearing
transaction)
Shape
(acquired by
Tetralogic)
Metamark
NKT
($35M raised; Therapeutics
New Mgt)
(Third Party)
DNAR
Oncomethylome/
MDxHealth
(IPO in Brussels
Stock Exchange)
Aileron
>$110M
raised
Alive, funded
GateKeeper
(rights acquired
by Clovis)
2010
Acetylon
(Raised
$52M;
$100M
Celgene
option to
buy)
Ligon Discovery
(Third Party)
Alive but no Investment
2011
2012
2013
Tensha
(Series A)
Ember
(Third Rock
Funded)
Syros
($30M
Series A)
OncoPep
(Funded
Series A)
Costim
(Acquired by
Novartis)
SixOne
Solutions
(Third
Party)
Margaux
(funded by
Angel
Investor)
Genometry
(Third Party)
Crowd-sourced
Not Alive Successful exit
Success: PD-1 and PD-L1
PD-1 and PD-L1 inhibition: example of bench to business to bedside
–
–
–
–
Dr. Gordon Freeman’s work
Large patent portfolio
Licensed non-exclusively to several companies
5 most promising drugs in clinic; Merck drug approved 9/4/14
Collaboration models
Virtual startup model
Clinical +
preclinical
work on
compounds
Develop
compounds
with Centers
and labs
Traditional
licensing and
sponsored
research
Sponsored
research with
groups of
investigators
Identify and
validate
targets
ORTV Mission: Bring Drugs to
the Clinic to benefit Patients
Multiple avenues to
collaborate with industry:
Collaborating with DFCI
O. Prem Das, PhD
Inna Nusinzon, PhD
Chief Research Business Development Officer
Technology Transfer Specialist
Office of Research and Technology Ventures
Office of Research & Technology Ventures
Dana-Farber Cancer Institute, BP309
Dana-Farber Cancer Institute, BP 304D
450 Brookline Ave, Boston, MA 02215
450 Brookline Ave, Boston, MA 02215
Phone: (617) 632-5893
Phone: (617) 582 7223
Fax: (617) 632-4012
Fax: (617) 632-4012
[email protected]
[email protected]
http://www.dana-farber.org/Research/Technology-Transfer.aspx