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.