Lili M. Portilla, MPA
Director, Office of Strategic Alliances
National Center for Advancing Translational Sciences (NCATS), NIH
16th Annual NIH SBIR/STTR Conference, Oct 21 – 23, 2014
Email: Lili.Portilla@nih.gov
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.
NCI
NHLBI
NIAID
OD
NIDCR
NEI
NIDA
NIA
CC
NIAMS
NIDDK
NLM
CIT
FIC
NCATS
NHGRI
NICHD
NIEHS
NINDS
NIBIB
NIAAA
NIMH
NIDCD
CSR
NCCAM
NINR
NIGMS
NIMHD

Therapeutics for Rare and Neglected
Diseases (TRND)

Bridging Interventional Development Gaps
(BrIDGs)

Molecular Libraries Probe Production Center

Assay Development

Toxicology in the 21st Century (Tox21)
DPI currently has 200+ collaborations with investigators across the U.S.
and around the world.



DPI is administratively intramural

No independent PIs, no tenure system

All projects are collaborations, 90% of which are with extramural
investigators/foundations/companies

Projects are selected via solicitation/review
Science is intermediary between mechanistic research and
commercialization

“Adaptor” function

Each project has tangible deliverable and technology/paradigm
development components
It is disease agnostic, works across disease spectrum


Common mechanisms and principles to make translation
better/faster/cheaper for all
Focuses on new technologies, enabling tools, dissemination

Activities facilitated through in-house drug
development experts and contracts
New indications for clinical stage drugs and
repurposing approved drugs
Medicinal chemistry
Rare disease bioassay development
Efficacy, pharmacology, ADME, toxicology, PK/PD
Compound scale-up, formulation
Clinical and regulatory development strategy, natural
history studies assessments
First in human clinical trials
NCATS DPI: A Collaborative Pipeline






Founded 2004, as part of MLP
~ 90 scientists
collaborations with investigators worldwide
Assay development, HTS, chemical
informatics, medicinal chemistry: “target to
lead”
Focus is unprecedented targets,
rare/neglected diseases
Mission



Chemical probes/leads
New technologies/paradigms to improve efficiency
and success rates of target-to-lead stage of drug
development
Chemical genomics: general principles of small
molecule – target interactions
The ADST Laboratory focuses on the development of a more efficient gateway to the
drug discovery paradigm through evaluation, development, and refinement of assay
strategies and technologies in collaboration with key experts and stakeholders.
Create/guide the primary and follow-up assay portfolio needed in the pursuit
of therapeutics discovery and development for rare and neglected diseases.
 Current pilot projects:
•
Peripheral and Optic neuropathies
―Charcot-Marie-Tooth Disease (CMT)
― Retinitis pigmentosa & Glaucoma
•
Erythroblastopenia
―Diamond–Blackfan Anemia (DBA)
•
Parasitic infections
•
•
•
Foundations’ gifts
CRADAs, RCAs
In-kind research support
―Lymphatic filariasis & Onchocerciasis
―Malaria
 Funding Mechanisms: Highly Collaborative
Goal: To formalize this resource through a
program/solicitation for assay development for
rare and neglected diseases (AD-RND).
Toxicology Technology Development:
The Tox21 Program
•
The goal is to quickly and efficiently test whether certain chemical compounds have the potential to disrupt
processes in the human body that may lead to adverse health effects.
Goals of Program:
1. Identify mechanisms of compound-induced biological activates
2. Prioritize chemicals for more extensive toxicological evaluation
3. Develop predictive models for biological response in humans
•
Once an assay is approved through a solicitation process, NCATS optimizes, validates, and screens a
specially designed library of environmentally relevant compounds; roughly 11,000 compounds are screened
by quantitative-High Throughput Screening for each approved assay.
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
Active BrIDGs Projects
Applicant
Organization Name
Org Type
Agent
Dis Type
Funding
Au, Jessie
Optimum Therapeutics
Small
business
Small Molecule
Bankiewicz, Krys
University of California San
Francisco
Academic
Gene Vector
Bloch, Kenneth
Massachusetts General Hospital
Academic
Small Molecule
Darling, Thomas
Edunn Biotechnology
Small
business
Oligonucleotide
Alzheimer's disease
CF/NIA
De Leon, Diva
Children's Hospital of Philadelphia
Academic
Peptide
Hyperinsulinism
Common Fund
Donn, Karl
Parion Sciences, inc.
Small
business
Small Molecule
Chronic dry eye
Common Fund
Academic
Peptide
Multiple sclerosis
Common Fund
Academic*
Gene Vector
Osteoarthritis
Common Fund
Dowling, Peter
Evans, Chris
University of Medicine and
Dentistry of New Jersey
Beth Israel deaconess Medical
Center
Pancreatic Cancer
Aromatic L-amino
acid decarboxylase
FOP & Anemia of
Inflammation
Common Fund
CF/NINDS
CF/NIAMS/NIDDK
Hebel, Henry
Terapio Corporation
Small
business
Large Protein
Acute Radiation
Syndrome
CF/NIAID
Katz, Laurence
University of North Carolina at
Chapel Hill
Academic*
Small Molecule
Combination
Acute Brain Injury
Common Fund
Kunos, George
NIH/NIAAA
Intramural*
Small molecule
Metabolic syndrome
Common Fund
MacDonald, Brian
Merganser Biotech LLC
Small
business
Peptide
Beta Thalassemia
CF/NINDS
Mannstadt,
Michael
Massachusetts General Hospital
Academic*
Peptide
Hypoparathyroidism
Common Fund
Maynard, George
Axerion Therapeutics
Biologic
Spinal Cord Injury
CF/NINDS
Magruder. Judy
Signature Therapeutics
Small Molecule
Chronic Pain
NIDA
Mellon, Synthia
University of California San
Francisco
Academic
Small Molecule
Niemann-pick C
CF/NINDS
Rogawski, Mike
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.
Small
business
Peptide
Atherosclerosis
Common Fund
Small
business
Small
business
* indicates that the investigator is partnered with a company



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, Nonprofit, Government Lab, Biotech / Pharma

Ex-U.S. applicants accepted

20 projects through pilot phase & 4 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


SCD: IND filed 10/14/11, approved 11/10/11


Phase 1 trial in patients commenced 9/13/12
Initiated first natural history study


Phase I trial commenced 12/11
HIBM: Complete response filed 7/27/12, approved 8/24/12


Phase I trial commenced 9/11
HIBM: NIH Clinical Center, 1st patient enrolled September 2011
Every project is a unique Public-Private partnership

Many include foundation and patient advocacy input
Therapeutic Area /
Disease
Sickle Cell Disease
Collaborator(s)
Agent
Status
Aes-Rx, NHLBI
NME – Small Molecule
Clinical
Chronic Lymphocytic
Leukemia
Hereditary Inclusion Body
Myopathy
Niemann-Pick Type C1
Leukemia & Lymphoma Society,
University of Kansas
New Zealand Pharmaceuticals, NHGRI
Repurposed Drug – Small
Molecule
NME – Small Molecule
Clinical
Johnson & Johnson, Albert Einstein
College of Medicine, Univ. of
Pennsylvania, Washington Univ., NICHD,
NINDS , NHGRI
Repurposed Drug - Small
Molecule
Clinical
Duchenne Muscular
Dystrophy
Cryptococcal Meningitis
ReveraGen BioPharma
NME – Small Molecule
Preclinical
Viamet Pharmaceuticals, Inc.
NME - Small Molecule
Preclinical
Core Binding Factor
Leukemia
Autoimmune Pulmonary
Alveolar Proteinosis
Fibrodysplasia Ossificans
Progressiva
Schistosomiasis
Liu; NHGRI
Preclinical
Bloch; Massachusetts General Hospital
Repurposed Drug - Small
Molecule
Repurposed Drug Biologic
NME - Small Molecule
CoNCERT Pharmaceuticals
NME – Small Molecule
Preclinical
Creatine Transporter Defect
Lumos Pharma
NME - Small Molecule
Preclinical
Autosomal Dominant
Retinitis Pigmentosa (adRP)
Hypoparathyroidism
Bikam Pharmaceuticals
NME - Small Molecule
Preclinical
Eli Lilly & Co.
NME - Small Molecule
Preclinical
Retinitis Pigmentosa
Klassen; University of California - Irvine
Cell Based Therapy
Preclinical
LEOPARD Syndrome
Kontaridis;Beth Israel Deaconess Medical
Center
NME - Small Molecule
Preclinical
Trapnell; Cincinnati Children’s Hospital
Clinical
Preclinical
Preclinical
Intellectual Property
• Background IP: Any IP generated PRIOR to initiation of TRND
Collaboration are RETAINED by the Applicant as Background IP
• New IP: The potential for development of NEW, multi-party IP will
depend on the stage at which the project enters into Collaboration
with TRND. However, TRND Collaborators should anticipate that there
WILL BE joint IP development with NCATS employees.

Inventorship: Should NEW IP be generated during the TRND Collaboration,
inventorship will be determined according to U.S. patent law

Agreements: Various model agreements are available at NIH, through
which TRND Collaborations are initiated and governed. The CRADA
mechanism is the most commonly used for TRND projects.
 A CRADA or CRADA Letter of Intent will be expected to be executed before
TRND proceeds with the project plan
BrIDGs
TRND
Contract Resource
Team-based Collaboration
PI must have identified lead agent
PI may start with lead optimized
No clinical trial support provided
Some clinical trial support
provided
IP retained by owner
TRND may generate IP
Universal disease scope
Rare and neglected diseases only
Investigator prepares IND
Regulatory affairs assistance
provided
Projects by Therapeutic Area
Projects by Drug Modality
CNS
Endocrinology
Small
Hematology &
Peptide
Cardiopulmonary
Infectious
Biologic
Disease
Musculoskeletal
Gene
Molecule
Vector
Oncology
Projects by Type of Collaborator
Academia
Government
Upon Entry
Current Status
Discover
y
Preclinic
al
IND
Enabling
IND/Clinic
Therapeutics Development Branch Statistics
58 Projects Adopted
7 projects
discontinued
due to No-Go’s
● 4 clinical trials initiated
● 17 INDs – 100% success
rate upon filing w/FDA
34 Ongoing Projects
20 projects
completed all
requested
tasks
Website: www.ncats.nih.gov
Facebook: facebook.com/ncats.nih.gov
Twitter: twitter.com/ncats_nih_gov
YouTube: youtube.com/user/ncatsmedia
E-Newsletter: ncats.nih.gov/news-andevents/e-news/e-news.html
Email us: info@ncats.nih.gov