Post on 07-Mar-2021
NCATS: Catalyzing Translational
Innovation
CHARLES NIEBYLSKI, PHD JDSTRATEGIC ALLIANCES MANAGER
New Approaches and Incentives in Drug DevelopmentDuke University School of LawNational Academy of Sciences, November 22, 2013
Standard Model
Basic Laboratory
Research
Clinical
Research
Translational
Research
Population
Research
Improved
Public
Health
The Way It Should Work
Basic Laboratory
Research
Patient-oriented
Clinical Research
Population-based Clinical
Research
Clinical Trials
Improved Public Health
“Houston, we have a problem”
• Fundamental science unprecedentedly
advanced, but:
– Poor transition of those advances to
interventions that tangibly improve human
health
– Drug/device development system in crisis
– Clinical trials system in crisis
– Poor adoption of demonstrably useful
interventions
People unhealthier and funders of biomedical research enterprise (public and private) impatient
NCATS Mission
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.
Catalyzing Collaborations Within NIH
NEI
NCI NHLBI NIAID
NIDCR
NIDDKNIAMS
NIDA
CIT
NIEHS
NIMH
NINDS
NCATS
NCCAM
NIMHD
NIDCD
NIGMSNINR
NIAAA
NICHD
NLM
CC
OD
NIA
NHGRI
FIC
NIBIB
CSR
Catalyzing Collaborations Outside NIH
NCATS
Biotech
Academia
PharmaNon-
Profits
Advocacy
Groups
Complements ― does not compete ― with the work of others
Revolutionizes the process of translation by promoting innovative research
Galvanizes and supports new partnerships
Supports and augments regulatory science and its application
Expands the precompetitive space
Characteristics of NCATS Initiatives
and Programs
• Address significant bottlenecks in the process
of translation
• Highly collaborative across NIH, other
government agencies, and with the private
sector.
• Quick to respond to needs of biomedical
researchers
• Collaborate with Domain Experts to help solve
their problems
• Therapeutics for Rare and Neglected
Diseases (TRND)
• Toxicology in the 21st Century (Tox21)
• Bridging Interventional Development Gaps
(BrIDGs)
• Molecular Libraries Probe Production Center
• Assay Development
Division of Pre-Clinical Innovation (DPI)
DPI currently has 300+ collaborations with investigators across the U.S. and around the world.
NCATS’ DPI Staff
Scientific and Admin
Management Lab Operations Automation and Cmd
Mgt
Chemistry
Informatics
Assay Development
and Biology
DPI is Different in Science and Operation
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
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
>440,000 compounds in library
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
Being re-tooled for 2014 and beyond***
NCATS Pharmaceutical Collection
Drug Source In house In procurement Total
US FDA 1676 141 1817
UK/EU/Canada/Japan 807 126 933
Total Approved 2391 359 2750
INN* 929 3952 4881
Total 3319 4312 7631
Informatics sources for NPC– US FDA: Orange Book, OTC, NDC,
Green Book, Drugs@FDA– Britain NHS– EMA– Health Canada– Japan NHI
Physical sources for NPC– Procurement from >70 suppliers
worldwide– In-house purification of APIs from
marketed forms– Custom synthesis
* International Nonproprietary Names (INN) Listing of Generics
Two approaches to therapeutics for rare
and neglected diseases
ClinicalTrials
LeadLead
Optimization
PreclinicalDevelopment
HitScreenTarget FDA approval
>300,000 compounds, 10-15 yrs
3000 drugs
3 years?
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
• 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
Bridging Interventional Development Gaps (BrIDGs) Program
BrIDGs Highlights
• 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
• 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
• 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
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
Comparison of BrIDGs and TRND
Tissue Chips for Drug Screening, a.k.a.:Microphysiological Systems (MPS) Program
• Goal» Develop chip to screen for safe, effective drugs
o Liver, heart, lung, other cell types
o Designed for multiple different readouts
• NIH, DARPA contribute ~$70M each over 5 years » NCATS and DARPA independently manage, fund separate
but highly coordinated program
» FDA provides regulatory science guidance
• Awards announced in 2012» Supporting the best ideas in engineering, biology, and
toxicology
Discovering New Therapeutic Uses for
Existing Molecules (Therapeutics Discovery)
NIH - Industry Pilot Program: Launched May 2012
NIH
CRAIndustry Partner
Researcher
Patients
Clinical and Translational Science Awards are
led by NCATS Division of Clinical Innovation
CTSAs:
• Support a national consortium of medical research institutions
• Work together to improve the way clinical and translational research is conducted nationwide
• Accelerate the research translation process
• Provide robust training for clinical and translation researchers
• June 2013 Report: IOM Vision for CTSAs in the changing landscape
Clinical and Translational Science Awards
(CTSA) Program Sites
NCATS DPI: A Collaborative Pipeline
Keeping an Eye on the Prize:Market Exclusivities
• Weigh commercialization potential with each translational advance
• Costs of de-risking hurdles (science, IP, market, & regulatory) is incentivizedprimarily by the potential for market exclusivity
Hurdles to be De-Risked Market Exclusivity
RewardsScience IP Market Regulatory Payor
Validity
On-Target
Off-Target
Assays
Models
FTO
Compositions
Method claims
New Formulations
Diagnostics
Un-met need
Patient buy in
Doctor buy in
Payor buy in
Scalable
Known Path
Known Cost
Patient scope
Follow-on drugs
Reimbursable Patent
- term remaining
- claim type & scope
- follow-on IP
- significant improvements
Off-Patent
-strategy addresses off-label use
FDA
-orphan
-pediatric
-break-through
-other
Data
-intangibles
Collaborative stakeholder models tend to increase the opportunity to overcome more of these risks. But such models have little direct effect on exclusivity designations.