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Brought to you by the Science/ AAAS Custom Publishing Office
Don't get lost in translation: How smart
design and technology are enabling bench-
to-bedside in translational research
October 14, 2015
Webinar Series
Sponsored by
Bruce Levine, Ph.D.
University of Pennsylvania
Philadelphia, PA
Laurence Cooper, M.D., Ph.D.
MD Anderson Cancer Center, Houston, TX
ZIOPHARM Oncology, Boston MA
Participating experts
Chris Ramsborg, Ph.D.
Juno Therapeutics
Seattle, WA
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October 14, 2015
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Sponsored by
Bench to Bedside Translation of
Redirected Immunity to Treat
Relapsed/Refractory Cancers
Bruce Levine, Ph.D.
Barbara and Edward Netter Professor in Cancer Gene Therapy
Department of Pathology and Laboratory Medicine
University of Pennsylvania
• Declaration of financial interest due to intellectual
property and patents in the field of cell and gene
therapy.
• Funding support for trials: ACGT, LLS, NCI,
Lustgarten Foundation and Novartis
• Conflict of interest is managed in accordance with
University of Pennsylvania policy and oversight
Conflict of Interest Statement
Cancer Immunotherapy
Problem 1: The enemy is ourselves
Problem 2: Cancer-specific immune
cells are very rare, if present at all
Problem 3: Cancer induced immune
suppression and immune evasion
Overcoming the Scarcity of Tumor Specific Immunity and Tumor Suppression: Creation of Re-directed T cells
TCR heterodimer “CAR” – a molecular chimera - off the shelf
- MHC independent
Extracellular
Intracellular
Chimeric Protein
Tumor binding domain
Evolution of Chimeric Antigen Receptor Design
Using Synthetic Biology to Overcome Tolerance
Extracellular
Intracellular
ζ
First Generation
CD4 / CD8z CARs
VH
VLV
L
VHV
H
VLV
L
VH
ζ ζ
First Generation
scFv CARs
VH
VLV
L
VHV
H
VLV
L
VH
Second Generation
scFv BBz CARs
ζ ζ
4-1BB
Finney, 2003
Imai, 2004
Milone, 2009
Carpenito, 2009
CD28
VH
VLV
L
VHV
H
VLV
L
VH
Second Generation
scFv CD28z CARs
ζζ
Roberts, 1995
Finney, 1998
Maher, 2002
CD27
ICOS
VH
VLV
L
VHV
H
VLV
L
VH
Second Generation
scFv CD27z CARs
scFv ICOSz CARs
ζζ
Song, 2012
Guedan, 2014
Duong, 2013
Kuwana, 1987
Eshhar, 1993
Irving & Weiss, 1991
Letourneur, 1991
Romeo, 1991
J Immunol 1997; 159: 5921
Science 1997; 276: 273
Immunol. Rev. 1997; 160: 43
Anti-CD3 Anti-CD28
Artificial APC: Bead
Signal 1
Growth
CD28 CTLA4 TcR/CD4
+
Bead Based in vitro T Cell Culture System
Gene Delivery For Permanent CAR Expression
Lentiviral (HIV-1 based) vectors- advantages over other vector types
including murine leukemia viruses:
•Efficiently transduce primary cells
•Long term stable gene expression without gene silencing that
occurs at high levels in oncoretroviral vectors
•Favorable safety profile
Levine, BL, PNAS 2006;103(46):17372
McGarrity, GJ, J Gene Med 2013; 15: 78
Gene Delivery For Temporary CAR Expression
•Currently much faster and cheaper than manufacture of viral
vectors
• In some settings, repeated infusion of temporary CAR’s may
be sufficient to treat disease
•Currently primarily a tool for assessing new tumor targets,
CAR designs, trial designs
Zhao, Y, Cancer Res. 2010;70(22):9053
Beatty, GL, , Cancer Immunol Res. 2014;2(2):112
CAR Expression via RNA
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
T cell
CD19
Native TCR
Tumor cell
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
Lentiviral vector
T cell
CD19
Native TCR
Tumor cell
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
T cell
CD19
Native TCR
Tumor cell
Lentiviral vector
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
T cell
CD19
Native TCR
Tumor cell
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
Anti-CD19 CAR construct
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
Anti-CD19 CAR construct
Targeting CD19+ CLL with CAR-Modified T cells
• CARs combine an
antigen recognition
domain of antibody with
intracellular signaling
domains into a single
chimeric protein
• Gene transfer (lentiviral
vector) to stably express
CAR on T cells confers
novel antigen specificity
CAR, chimeric antigen receptor
TCR, T-cell receptor.
Anti-CD19 CAR construct
CTL019 cell
Dead tumor cell
Robust CAR T Cell Production Process
Complete & Partial Responses in
Relapsed/Refractory CLL
New Engl J Med 365:725, 2011, Science Translational Med 3:95ra73, 2011
CLL is an indolent disease – Can CAR T cells work in rapidly
growing malignancies?
April, 2012 Pediatric ALL 1st Patient
Karyotype: high risk
Dx 5/2010, R1: 10/2011,R2: 2/2012
3/2012: high dose
cytoxan/clofaribine: persistent ALL
Marrow 4/16/2012: 60% blasts
w/kidney, liver, spleen lesions
CAR T cells infused with no
additional chemotherapy
April, 2012 May, 2015
May, 2015
Center For Advanced Cell Therapy
Developing a Clinical Algorithm:
Management of CAR T Cell Toxicities
• B cell aplasia
• observed in all responding patients to date
• managed with IV immune globulin replacement
therapy
• Tumor Lysis syndrome
• Cytokine release syndrome (CRS)
• reversible, on-target toxicity
• Controlled with anti-IL-6 therapy (tocilizumab) • Grupp, SA et al. N Engl J Med. 2013 Apr 18;368(16):1509
• Lee, DW et al. Blood. 2014 Jul 10;124(2):188
• Severity related to tumor burden
The First CAR Assembly Lines
Modern CAR Assembly Lines
Penn Platform Technology:
Allows design and targeting against other tumors
Chimeric Antigen Receptor T Cell Translation:
Key Points (I)
•Engineered CAR T cells are a dividing drug and
persist for years providing functional immunity –Sci Transl Med. 2015 Sep 2
•CTL019 CARs have potent activity in refractory
ALL, CLL, DLBCL, FL, myeloma –Sci Transl Med. 2011, NEJM 2011, NEJM 2013, NEJM 2014, NEJM
2015
•CARs targeting antigens in solid tumors are
promising in early stage trials
Chimeric Antigen Receptor T Cell Translation:
Key Points (II)
•Tech transfer from academia (Penn) to industry
(Novartis) accomplished
•Novartis now manufacturing for the pediatric r/r
ALL global clinical trial and the DLBCL global
clinical trial in the US
–Will be expanded into other countries in the
second half of 2015.
CAR Clinical Trials in Philadelphia
http://www.penncancer.org/Tcelltherapy
Lentiviral vector CAR’s • Adult Acute Lymphoblastic Leukemia NCT02030847
• Chronic Lymphocytic Leukemia NCT01747486
• Adult Lymphomas: NCT02030834
• Myeloma: NCT02135406 (CART19), NCT02546167 (BCMA)
• Pediatric Leukemia and Lymphoma: NCT01626495
• Glioblastoma: NCT02209376
• Mesothelin expressing cancers: NCT02159716 (CARTmeso),
NCT02465983 (CARTmeso19)
• Multi-center CTL019 trials 8 sites enrolling NCT02228096
RNA CAR’s • Mesothelioma: NCT01355965
• Pancreatic Cancer: NCT01897415
• Breast Cancer: NCT01837602
• Hodgkin’s Lymphoma: NCT02277522
• AML: pending
• Neuroblastoma: pending
CAR Clinical Trials in Philadelphia
http://www.penncancer.org/Tcelltherapy
To Date
>200 CTL019 Patients
>40 other CAR’s
Lentiviral vector CAR’s • Adult Acute Lymphoblastic Leukemia NCT02030847
• Chronic Lymphocytic Leukemia NCT01747486
• Adult Lymphomas: NCT02030834
• Myeloma: NCT02135406 (CART19), NCT02546167 (BCMA)
• Pediatric Leukemia and Lymphoma: NCT01626495
• Glioblastoma: NCT02209376
• Mesothelin expressing cancers: NCT02159716 (CARTmeso),
NCT02465983 (CARTmeso19)
• Multi-center CTL019 trials 8 sites enrolling NCT02228096
RNA CAR’s • Mesothelioma: NCT01355965
• Pancreatic Cancer: NCT01897415
• Breast Cancer: NCT01837602
• Hodgkin’s Lymphoma: NCT02277522
• AML: pending
• Neuroblastoma: pending
Study Participants
Abramson Cancer Center
Center for Cellular Immunotherapies
Director, Carl June
Clinical Cell and Vaccine Production Facility
Process Development and Correlative Studies Laboratory
Department of Medicine
Department of Pathology and Laboratory Medicine Division of Transfusion Medicine and Therapeutic Pathology
Brought to you by the Science/ AAAS Custom Publishing Office
Don't get lost in translation: How smart
design and technology are enabling bench-
to-bedside in translational research
October 14, 2015
Webinar Series
Sponsored by
Bruce Levine, Ph.D.
University of Pennsylvania
Philadelphia, PA
Participating experts
Chris Ramsborg, Ph.D.
Juno Therapeutics
Seattle, WA
Laurence Cooper, M.D., Ph.D.
MD Anderson Cancer Center, Houston, TX
ZIOPHARM Oncology, Boston MA
Cost-effective T-cell-based immunotherapies for
cancer October 14, 2015
Webinar Title: Don't get lost in translation: How smart design and technology are enabling bench-to-bedside in
translational research
Science/AAAS
Some of technology described was advanced through research conducted at the MD Anderson Cancer Center by Laurence Cooper, M.D., Ph.D. Both MD Anderson Cancer Center and Dr. Cooper have a financial interest in ZIOPHARM Oncology, Inc., and Intrexon Corporation. On May 7, 2015, Dr. Cooper was appointed as the Chief Executive Officer at ZIOPHARM. Dr. Cooper is now a Visiting Scientist at MD Anderson where he will continue to supervise the development of this technology.
T cells genetically modified with tumor-specific CAR or TCR
Clinical & Translational Immunology (2014) 3, e16;
Organization Immunology
Bioprocessing
Manufacturing Clinical conduct
Correlative studies
Regulatory
Bench Bedside
Approaches to manufacture and distribution of engineered T cells
Approaches to manufacture and distribution of engineered T cells
The 3 “P”s
Procurement Process Product
The 3 “P”s
Procurement Process Product
Avoid technology that relies on single source vendors
The 3 “P”s
Procurement Process Product
Avoid technology that relies on single source vendors
Innovation versus
continuation
The 3 “P”s
Procurement Process Product
Avoid technology that relies on single source vendors
Innovation versus
continuation Scalable
Procurement
• Tumor infiltrating lymphocytes
• Venipuncture
• Apheresis
• Select/sort • T-cell “starting” population
Process #1: Gene transfer
• Viral • Retrovirus
• Lentivirus
• Non viral • DNA
• mRNA
Process #2: Propagation
• Non-specific • Cross-link CD3
• Cross-link co-stimulatory molecules
• Antigen-specific • Tumor-associated antigen
• CAR
• Cell-free or cell-based • Beads
• K-562
K-562-derived activating and propagating cells (AaPC)
Genetically-modified K-562 cells
NK cells gd T cells
Treg cells ab T cells (TIL)
TH17 cells NKT cells
Immunol Rev. 2014 Jan;257(1):181-90
Criteria to produce a master cell bank of aAPC
Parameter Test
Endotoxin LAL <5 EU/mL
Sterility Direct inoculation method
Viruses
Replication-competent lentivirus
In vitro and in vivo culturing
Bovine 9CFR in vitro assay
PCR for human viruses and Bovine polyoma virus
Quantitative product enhanced reverse transcriptase (Q-PERT)
assay for retroviruses
Mycoplasma Test for presence of agar-cultivable and non-agar cultivable
mycoplasma
Identity
Transmission electron microscopic examination
Isoenzyme Analysis
DNA fingerprinting
Immunophenotyping (gated flow cytometry)
Viability 70%
Introduced cell surface antigen(s) 40%
CD32 75%
Product
3rd
party T cells RecipientsDonor
RecipientDonor
Autologous
Allogeneic
Dual distribution approaches for T-cell immunotherapy
Off-th
e-sh
elf (O
TS) P
atie
nt
Spe
cifi
c
Centralized Point-of-care (POC)
Genetically modified T cells
One patient Multiple Patients
Autologous T cells Allogeneic T cells
Near real time In advance of need
Disease cure Disease control
CAR
Patient
TCRαβ
Eliminating TCR on CAR+ T cells
Blood. 2013 Aug 22;122(8):1341-9 Blood. 2012 Jun 14;119(24):5697-705
CAR
Patient
TCRαβ
Normal cells
HLAs
Eliminating TCR on CAR+ T cells
Blood. 2013 Aug 22;122(8):1341-9 Blood. 2012 Jun 14;119(24):5697-705
CAR
Patient
CD19
Intended response
B-cell leukemia/lymphoma HLAs
TCRαβ
Normal cells
HLAs
Eliminating TCR on CAR+ T cells
Blood. 2013 Aug 22;122(8):1341-9 Blood. 2012 Jun 14;119(24):5697-705
CAR
Patient
CD19
Intended response
B-cell leukemia/lymphoma HLAs
TCRαβ
Eliminating TCR on CAR+ T cells
Blood. 2013 Aug 22;122(8):1341-9 Blood. 2012 Jun 14;119(24):5697-705
CAR
Patient
CD19
Intended response
B-cell leukemia/lymphoma HLAs
TCRαβ
Gene insertion:
Retrovirus/lentivirus
Sleeping Beauty
mRNA
Artificial nuclease
Eliminating TCR on CAR+ T cells
Blood. 2013 Aug 22;122(8):1341-9 Blood. 2012 Jun 14;119(24):5697-705
Personalized Therapy for Disease and Patient
Infuse T cells with more than one specificity Personalized for the disease
Intra-tumor Inter-tumor
Heterogeneity of tumor-associated antigen (TAA)
Infuse T cells with one or more specificity Personalized for the patient
“N=1” trial paradigm
Power-law curve The new industrialization of T cells
Number of trials
Nu
mb
er o
f p
atie
nts
Power-law curve The new industrialization of T cells
Number of trials
Nu
mb
er o
f p
atie
nts
Traditional Med Centers
Power-law curve The new industrialization of T cells
Number of trials
Nu
mb
er o
f p
atie
nts
Traditional Med Centers
Immuno-oncology at Med Centers
Power-law curve The new industrialization of T cells
Cost of distribution
Number of trials
Nu
mb
er o
f p
atie
nts
Traditional Med Centers
Immuno-oncology at Med Centers
Power-law curve The new industrialization of T cells
Cost of distribution
Number of trials
Nu
mb
er o
f p
atie
nts
Traditional Med Centers
Immuno-oncology at Med Centers 1
Points to consider
• No-single source failure
• Keep-it-simple
• Non viral
• Keep it simple
Put in un graphic
Acknowledgements
Brought to you by the Science/ AAAS Custom Publishing Office
Don't get lost in translation: How smart
design and technology are enabling bench-
to-bedside in translational research
October 14, 2015
Webinar Series
Sponsored by
Bruce Levine, Ph.D.
University of Pennsylvania
Philadelphia, PA
Participating experts
Chris Ramsborg, Ph.D.
Juno Therapeutics
Seattle, WA
Laurence Cooper, M.D., Ph.D.
MD Anderson Cancer Center, Houston, TX
ZIOPHARM Oncology, Boston MA
September 2015 Juno Therapeutics
How product knowledge enables process scale-up/out.
Proprietary Materials
Juno Therapeutics 70 Proprietary Materials
Forward-Looking Statements
This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties, and assumptions. If
the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by
such forward-looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited
to, any expectations regarding investment returns; any projections of financial information; any statements about historical results that may suggest
trends for our business; any statements of the plans, strategies, and objectives of management for future operations, including our manufacturing
and process development; any statements of expectation or belief regarding future events, potential markets or market size, technology
developments, our product pipeline, clinical data, enforceability of our intellectual property rights, competitive strengths or our position within the
industry; any statements regarding the anticipated benefits of our Celgene collaboration or other strategic transactions; and any statements of
assumptions underlying any of the items mentioned.
These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future
performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited
to, risks associated with: the success, cost, and timing of our product development activities and clinical trials; our ability to obtain regulatory
approval for and to commercialize our product candidates; our ability to establish a commercially-viable manufacturing process and manufacturing
infrastructure; regulatory requirements and regulatory developments; the effects of competition and technological advances; our dependence on
third-party collaborators and other contractors in our research and development activities, including for the conduct of clinical trials and the
manufacture of our product candidates; our dependence on Celgene for the development and commercialization outside of North America of product
candidates for which Celgene exercises an option; our ability to obtain, maintain, or protect intellectual property rights related to our product
candidates; among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in
these forward-looking statements, as well as risks relating to our business in general, see our Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission on August 14, 2015 and our other periodic reports filed from time to time with the Securities and Exchange
Commission. Except as required by law, we assume no obligation and do not intend to update these forward-looking statements or to conform these
statements to actual results or to changes in our expectations.
Juno Therapeutics 71 Proprietary Materials
FOUNDING INSTITUTIONS
ACADEMIC PARTNERS
Translating Research into Clinical and Commercial Products
• Juno Therapeutics has a network of founding institutions and academic partners.
• This network provides insights into the process of translating novel research into clinical products (including clinical manufacturing)
• My expertise is in product and process development. – Research -> Early Phase – Early Phase -> Late Phase – Late Phase -> Commercial
Juno Therapeutics 72 Proprietary Materials
Scaling-Up/Out Requires Product and Process Knowledge
Product Knowledge: Which product attributes are important for biological activity (safety and efficacy) of product.
Process Knowledge: Understanding the combination of process parameters and material attributes required to manufacture the desired product.
Moving any bioprocess (cell therapy or otherwise) into a multi-product manufacturing setting requires the product/process knowledge to establish a process robust enough that it can be repeatably executed (process control).
Building process knowledge and a process control strategy to enable transfer to a moderately-sized multi-product facility is resource intensive.
In most cases it is not feasible or cost effective to build this amount of process knowledge prior to demonstrating efficacy in the clinic.
Juno Therapeutics 73 Proprietary Materials
Recommendations for institutions and companies in early-phase development
1. Focus on building product knowledge.
2. Invest is translational infrastructure and knowledge management.
– Centralized databases to store and compare clinical, translational and manufacturing data.
– Organizational structures to enable cross-functional collaboration between scientific and non-scientific functions.
3. Document, Document, Document
– Manufacturing Batch Records – Store analytical data (manufacturing, translational) in a thoughtful way. – Know and document source of all raw materials (e.g. cell lines, plasmids).
Juno Therapeutics 74 Proprietary Materials
Engineered T-Cell Product Knowledge
Adoptive immunotherapy for cancer: harnessing the T cell response
Nicholas P. Restifo, Mark E. Dudley & Steven A. Rosenberg
Nature Reviews Immunology 12, 269-281 (April 2012)
doi:10.1038/nri3191
Product Knowledge can be developed via a product characterization effort.
• Phenotype
• In Vitro Function
• In Vivo Function
Juno Therapeutics 75 Proprietary Materials
Invest is translational infrastructure and knowledge management
Median DFS for patients in CR:
Cy±VP16 = 150 days
Flu/Cy, not reached
CR = 17/17
MRD negative CR = 16/17
DFS = disease-free survival; DL2 = dose level 2; Flu/Cy = fludarabine & cyclophosphamide; CR = complete response; MRD =
minimal residual disease
Data for JCAR014 in Adult R/R ALL
Juno Therapeutics 76 Proprietary Materials
Recommendations for institutions and companies in early-phase development
4. Invest in translational sample inventory system – Take multiple drug product, in process, raw material, translational (Clinical)
samples from all products. – Aliquot and store samples in multiple formats (Cell-based assays,
transcriptional analysis (e.g. NGS), mass spectroscopy). – Run small proof of concept studies to demonstrate sample suitability and
stability.
5. Use stored samples to help elucidate mechanisms and
attributes that discriminate response and safety in products demonstrating activity.
Product Knowledge can be developed after clinical proof-
of-concept has been established using sample inventory.
Juno Therapeutics 77 Proprietary Materials
Clinical evidence and product knowledge will justify investment in process knowledge
Resolu' on)of)Advanced)Lymphoma)with)CD19)CAR)T)Cells))
Pre)CD)19)CAR?T)cell)infusion) 28)Days)Post)CD)19)CAR?T)cell)infusion)
Resolu' on)of)Advanced)Lymphoma)with)CD19)CAR)T)Cells))
Pre)CD)19)CAR?T)cell)infusion) 28)Days)Post)CD)19)CAR?T)cell)infusion)
Day 37 After CD19
CAR T Cells
ALL Patient Before CD19
CAR T cells
Day 28 After CD19
CAR T Cells
NHL Patient Before CD19
CAR T cells
Our early experience
in leukemia trials demonstrates 87%-
93% complete
remission rates
Our early experience
in lymphoma demonstrates 56%
overall response
rate (1)
(1) ORR of 62% for patients treated following cyclosphosphamide / fludarabine conditioning regimen.
.
Juno Therapeutics 78 Proprietary Materials
Ease of Scale-Up/Out scales with Product Knowledge
Building Product Knowledge early enables process changes between early- and late-phase trials as well as building process knowledge.
Process changes allow the deployment of new technologies that are suitable for a multi-product large-scale manufacturing environment. – Closed Systems – Fully-Defined Raw Materials
Wait until clinical proof-of-concept has been established before
investing in process knowledge, unless a platform process has been established for product class.
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Bruce Levine, Ph.D.
University of Pennsylvania
Philadelphia, PA
Participating experts
Chris Ramsborg, Ph.D.
Juno Therapeutics
Seattle, WA
Don't get lost in translation: How smart
design and technology are enabling bench-
to-bedside in translational research
October 14, 2015
Webinar Series
Sponsored by
Laurence Cooper, M.D., Ph.D.
MDACC, Houston, TX
ZIOPHARM Oncology, Boston MA
Look out for more webinars in the series at:
webinar.sciencemag.org
To provide feedback on this webinar, please e-mail
your comments to webinar@aaas.org
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Don't get lost in translation: How smart
design and technology are enabling bench-
to-bedside in translational research
October 14, 2015
Webinar Series
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