Partnerships with NIH
to Advance New Technologies
Cindy K. Fuchs, J.D.
Director, Technology Advancement Office, NIDDK
Lili M. Portilla, M.P.A.
Director, Office of Strategic Alliances, NCATS
AIPLA 2012 Annual Meeting
NIH Translational Research Resources
for Advancing Early Stage Technologies
Cindy K. Fuchs, J.D.
Director, Technology Advancement Office, NIDDK
Disclaimer: The information presented herein is not intended to be and
should not be construed as legal advice.
Translational Research Process
Product
Regulatory Approval
Clinical Trials
Preclinical Development
Lead Compound Optimization
Screen for Activity (Dr. Gold identified known drugs but no novel compounds)
Assay Development
1 New Medicine
Target Validation
Identify Molecular Target
10,000 Molecules
Common Translational Research Needs
• R&D Plan: unmet need, full commitment,
resources and capabilities (HTS, medchem,
relevant models, broad team-based expertise)
• IP Package: convert a basic research discovery
into a marketable product with a strong IP
portfolio to protect R&D investment
• Pre-clinical Package: de-risk technology (lead
optimization, toxicity, efficacy, etc.) to prove
clinical relevance and incentivize commercial
investment
PROOF OF CLINICAL RELEVANCE REQUIRED
Drug Discovery
Early
Discovery
Lead to
Pre-clinical
Candidate
Hit to Lead
Pre-clinical
Development
Clinical
Trials
Academia
Basic Science:
Identification of
Molecular Pathways
Target
Identification
Commercial Partnering Interest Has Shifted 1
Early Stage Research Discovery --> Pre-Clinical/Clinical Success
Biotech/Pharma Companies
Target
Validation
Assay
Development
1 Stewart,
------------------------------------------>
Validated
Hits
Lead
Drug
Candidate
New
Medicine
Preclinical and Clinical
Development
J., Campbell Alliance Dealmakers’ Intentions Survey 2012; Christini, A., Nat. Biotechnol. 30, 933-936 (2012)
PROOF OF STRONG IP REQUIRED
After Ariad v. Lilly (2010)
- Patents are not awarded for discovering key mechanisms no matter how groundbreaking
- Broad patent claims should be supported by a
representative number of working examples in specification
- Filing an application too early (with incomplete written
description) may reduce incentives for commercial partners
Options for Advancing Dr. Gold’s Technology
Traditional patent licensing model
- a broad mechanism of action claim not likely patentable under Ariad
- create R&D plan: design and evaluate novel analogs
- create IP package: file on novel analogs
- create pre-clinical package: lead optimization, pharm-tox, efficacy, etc.
New “drug re-purposing” model
-new use of known drugs –> typically limited commercial potential
exceptions: orphan drug status, new formulation (combination,
delayed release, etc.), off-label use
- highlights need for pre-competitive partnerships between academia,
non-profits, govt. labs, FDA, industry
Current Focus on “Translational Research”
K. Pienta, MD, Univ. Mich.
Nature Publishing Group
NIH Translational Research Addresses Unmet Needs
FDA
Regulatory
Science
Anti-Cancer Therapies
& Diagnostics
HIV Therapies
& Diagnostics
Vaccines, Drugs,
Diagnostics, Enhanced
Facilities/Workforce
NIH INTRAMURAL RESEARCH
(NIH Laboratories)
NIH EXTRAMURALRESEARCH
(Grantees and Contractors)
Alaska
5
Data: Assoc of University Technology Managers (AUTM) Survey 2004
Supports:
• Bethesda, MD; Arizona; Montana
• 27 NIH Institutes & Centers
• >6,000 scientists & research personnel
• Basic Translational & Clinical Research
• 10% of overall NIH budget
Courtesy of OER/NIH
Supports:
• >3,000 institutions worldwide
• >300,000 scientists & research personnel
• Awards issued in over 100 countries
• Basic Translational & Clinical Research
• 90% of overall NIH budget
NIH Intramural Translational Resources
NIH Intramural Laboratories – 27 Institutes & Centers (ICs)
• Each IC has a unique mission and is organized by
-
disease (cancer, diabetes)
organ system (heart lung & blood, eye)
life stage (child health, aging)
scientific discipline (infectious diseases, genomics)
• ICs employ world-class scientists
- potential research collaborations
- access to special patient populations
- research tools (cell lines, antibodies, mouse models)
Accessing NIH Intramural Translational Resources
• Managed by IC Technology Development Offices
- Facilitate research partnerships, exchange of research materials, data and
confidential information
- Negotiate transactional agreements:
o confidentiality agreements
o
clinical trial agreements
o
collaboration agreements, CRADAs
- Evaluate new innovations from IC scientists for partnering or patenting
- Provide strategic guidance to IC scientists on technology development
- Create virtual teams to advance early stage R&D and prove clinical relevance
• Contact Information - Handout
Accessing NIH Extramural Translational Resources
• Managed by IC Extramural Scientific Program Officers
- Financial: grants & contracts
- In-Kind (via NIH contracts/grants):
- Sample repositories
- Screening
- Preclinical development
- Clinical trial networks
• Specific Resource Program Information – Handout
For More Information…
Handouts:
• NIH Translational Research Resources
• NIH Intramural Researchers
• NIH Technology Development Offices
Contact Information:
cfuchs@mail.nih.gov
http://www2.niddk.nih.gov/TechDev/Main-HomePage/
Lili M. Portilla, MPA
Director of Strategic Alliances, NCATS
AIPLA 2012 Annual Meeting

Established on December 23, 2011

Part of Consolidated Appropriations Act 2012 (PL 112-74)
“To catalyze the generation of innovative methods
and technologies that will enhance the development,
testing, and implementation of diagnostics and
therapeutics across a wide range of human diseases
and conditions.”
COUNCIL/
CAN BOARD
OFFICE OF THE
DIRECTOR
Christopher Austin, M.D.
(Director)
Kathy Hudson, Ph.D.
(Acting Deputy Director)
OFFICE OF GRANTS
MANAGEMENT &
SCIENTIFIC REVIEW
EXECUTIVE OFFICE
Erin Shannon, M.B.A.
(Acting Executive Officer)
Jane Steinberg, Ph.D.
(Acting Director)
OFFICE OF RARE
DISEASES RESEARCH
Stephen Groft, Pharm.D.
(Director)
OFFICE OF POLICY,
COMMUNICATIONS
& STRATEGIC
ALLIANCES
Lili Portilla, MPA
(Acting Director)
DIVISION OF PRECLINICAL
INNOVATION
DIVISION OF
CLINICAL
INNOVATION
(Vacant)
Josephine Briggs, M.D.
(Acting Director)

Therapeutics for Rare and Neglected
Diseases (TRND)

Toxicology in the 21st Century (Tox21)

Bridging Interventional Development Gaps
(BrIDGs)

Molecular Libraries Probe Production Center

RNA interference (RNAi)
DPI currently has 300+ collaborations with investigators across the U.S.
and around the world.
NCATS DPI: A Collaborative Pipeline
Project Unvalidated Validated
target
Entry Point target
Target
Validation
Target
RNAi
Assay
Dev
Preclinical
development
candidate
Lead
compound
Target
assay
Lead
Probe/Lead
Development Optimization
Probe Devel/NCGC
Preclinical
Development
Clinical
development
candidate
Clinical Trials
I
II
III
Preclinical Development/TRND
Assay , Chemistry Technologies
BrIDGs
FDA Collaboration
DPI
Systems Toxicology (Tox21)
Repurposing
Repurposing
Paradigm/Technology Development
Genome-wide
RNAi systems
biology data
Deliverables
Chemical
genomics
systems biology
data
Leads for
therapeutic
development
Small molecule and siRNA
research probes
Approved drugs
effective for new
indications
Predictive in vitro
toxicology profiles
New drugs for
untreatable diseases
Drugs suitable for
adoption for further
development
Novel clinical
trial designs
More efficient/faster/cheaper translation and therapeutic development
FDA
approval
Bridging Interventional Development Gaps
(BrIDGs) Program

Model: Contract access collaboration between DPI and
extramural labs (Formerly NIH-RAID Program)

Projects
 Enter with clinical candidate identified
 Any disease eligible
 Gap analysis followed by data generation using DPI contracts to
generate data necessary for IND filing
 Exit at or before IND
 Milestone driven
 Therapeutic modalities: any (small molecules, peptides,
oligonucleotides, gene therapy, antibodies, recombinant proteins)

Eligible Applicants
 Academic (US and Ex-US), Non-Profit, SBIR eligible
businesses

180 applications submitted since 2005
 34 approved

19 completed projects (two in FY12)
 12/12 submitted INDs approved
 5 projects in Phase 1, three in Phase II
 5 agents licensed during or after BrIDGs involvement
BrIDGs Portfolio September 2012
Applicant
Organization Name
Org Type
Agent
Disease
Au, Jessie
Optimum Therapeutics
Biotech
Small Molecule
Bankiewicz, Krystof
University of California San
Francisco
Academic
Gene Vector
Bloch, Kenneth
Massachusetts General Hospital
Academic
Small Molecule
Darling, Thomas
Edunn Biotechnology
Biotech
Oligonucleotide
Alzheimer's disease
CF/NIA
De Leon, Diva
Children's Hospital of Philadelphia
Academic
Peptide
Hyperinsulinism
Common Fund
Donn, Karl
Parion Sciences, inc.
Biotech
Small Molecule
Chronic dry eye
Common Fund
Academic
Peptide
Multiple sclerosis
Common Fund
Academic*
Gene Vector
Osteoarthritis
Common Fund
Dowling, Peter
Evans, Christopher
University of Medicine and
Dentistry of New Jersey
Beth Israel Deaconess Medical
Center
Pancreatic Cancer
Funding
Aromatic L-amino
acid decarboxylase
FOP & Anemia of
Inflammation
Common Fund
CF/NINDS
CF/NIAMS/NIDDK
Kunos, George
NIH/NIAAA
Intramural*
Small molecule
Metabolic syndrome
Common Fund
Mannstadt,
Michael
Massachusetts General Hospital
Academic*
Peptide
Hypoparathyroidism
Common Fund
Mellon, Synthia
University of California San
Francisco
Academic
Small Molecule
Niemann-Pick C
CF/NINDS
Miller, Kenneth
Kemmx Corporation
Biotech
Small molecule
Rheumatoid arthritis
CF/NIAMS
Rogawski, Michael
University of California, Davis
Academic*
Small molecule
Epilepsy
CF/NINDS
Sutula, Thomas
University of Wisconsin Madison
Academic*
Small Molecule
Epilepsy
Common Fund
Turner, Scott
Kinemed, Inc.
Biotech
Peptide
Atherosclerosis
Common Fund
* indicates that the investigator is partnered with a company
Therapeutics for Rare and Neglected Diseases
(TRND) Program



Model: Comprehensive drug development collaboration between DPI
and extramural labs with disease-area / target expertise
Projects
 May enter at various stages of preclinical development
 Disease must meet FDA orphan or WHO neglected tropical disease
criteria
 Taken to stage needed to attract external organization to adopt to
complete clinical development/registration, max 2a
 Milestone driven
 Therapeutic modalities: small molecules, proteins
 Serve to develop new generally applicable platform technologies and
paradigms
Eligible Applicants
 Academic, Non-Profit, Government Lab, Biotech / Pharma
 Ex-U.S. applicants accepted
TRND Highlights
• 14 projects through pilot phase & 2 public solicitations since 2009
• Mix of small molecules and biologics
• Two innovative platform technologies
• 3 investigational drugs taken into humans
• CLL: IND filed with US FDA 7/12/11, approved 8/5/11
• Phase I trial commenced 9/11
• SCD: IND filed 10/14/11, approved 11/10/11
• Phase I trial commenced 12/11
• HIBM: Complete response filed 7/27/12, approved 8/24/12
• Phase 1 trial in patients commenced 9/13/12
• Initiated first natural history study
• HIBM: NIH Clinical Center, 1st patient enrolled September 2011
• Every project is a unique Public-Private partnership
• Many include foundation and patient advocacy input
TRND Portfolio
Active TRND Projects
Collaborator
Organization Name(s)
Partner Type(s)
Agent
Therapeutic Area / Disease
TRND Pilot Project
NPC-SOAR, Washington Univ., Einstein
College of Medicine, NICHD, NHGRI
Disease Foundation,
Academic, DIR
Repurposed
Approved Drug
Niemann-Pick C
TRND Pilot Project
New Zealand Pharmaceuticals, NHGRI
Biotech, DIR
Intermediate
Replacement
Hereditary Inclusion Body
Myopathy
TRND Pilot Project
Aes-Rx, NHLBI
Biotech, DIR
NME
Sickle Cell Disease
TRND Pilot Project
Leukemia & Lymphoma Society, Kansas
Univ. Cancer Center
Disease Foundation,
Academic
Repurposed
Approved Drug
Chronic Lymphocytic
Leukemia
Reeves, Erica
ReveraGen BioPharma
Small Business
NME
Duchenne Muscular Dystrophy
Campbell, David
Afraxis, Inc.
Small Business
NME
Fragile X Syndrome
Garvey, Edward
Viamet Pharmaceuticals, Inc.
Small Business
NME
Cryptococcal Meningitis
Liu, Paul
NHGRI
DIR
Repurposed
Approved Drug
Core Binding Factor Leukemia
Kimberlin, David
University of Alabama
Academic
Nucleotide
Analog Pro-drug
Neonatal Herpes Simplex
Trapnell, Bruce
Cincinnati Children’s Hospital
Academic
Biologic
Autoimmune Pulmonary
Alveolar Proteinosis
Bloch, Kenneth
Massachusetts General Hospital
Academic
NME
Fibrodysplasia Ossificans
Progressiva
Liu, Julie
CoNCERT Pharmaceuticals
Small Business
NME
Schistosomiasis
Davis, Robert
Lumos Pharma
Small Business
NME
Creatine Transporter Defect
Sazani, Peter
Sarepta Therapeutics
Small Business
Oligo (PMO)
Duchenne Muscular Dystrophy
ncats.nih.gov

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
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
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Partnerships with NIH
to Advance New Technologies
If you wish to receive an electronic version of this
presentation and/or referenced resources, please send
your request to: MTA@niddk.nih.gov
AIPLA 2012 Annual Meeting