RARE DISEASES RESEARCH AT NIHNCATS, TRND AND ATAXIA RESEARCH

John H. Ferguson MD, Medical Consultant, ORDR/NCATS/NIH

PRESENTER DISCLOSURES

No relationships to disclose or list

AGENDA

Rare Diseases Office of Rare Diseases Research

(ORDR) National Center for Advancing

Translational Sciences – NCATS Therapeutics for Rare and Neglegted

Diseases –TRND Ataxia research with ORDR, NCATS and

TRND

RARE DISEASES

18 - 25million people in the US are affected - Exact Prevalences Unknown

Estimated 6%-8% of Population Prevalence definition: < 200,000 people in the USA > 7000 Genetic and Acquired Rare Diseases Need Collaborative Efforts of the Rare Diseases Community

Academic Researchers Federal Research and Regulatory Programs > 1100 Patient Advocacy Groups/Philanthropic

Foundations Industry

Congressional Rare Diseases Caucus Established

RARE DISEASES CLINICAL RESEARCH NETWORK

19 Consortia supported by ORDR, NINDS, NIAMS, NICHD, NHLBI, NIDDK, NIAID, NIDCR and NCI

Required 3 diseases

longitudinal studies of patients,

Encouraged : Phase I, II and III  trials;

Training of Investigators in clinical research of rare diseases;

Pilot studies/demonstration projects

Collaboration with Patient Advocacy Groups Data Management Coordinating Center DMCC > 192 Institutions World-wide, 42 International Sites, > 200

Diseases 9393 patients enrolled in 68 studies

• Collaborative Clinical Research

• Public Resources and Education

• Centralized Data Coordination and

Technology Development

• Training

The Data Management and Coordinating Center

Coalition of PatientAdvocacy Groups

(CPAG)

Chronic Graft Versus Host Disease Consortium

CREATION OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)

To catalyze the development 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

Clinic AccessPhase

iv

DEVELOPMENT OF NEW THERAPEUTICS

Phase I

Phase III

Phase II

Stage 1Drug Discovery

Stage 2Pre-clinical

Stage 3Clinical Trials

Stage 4FDA Review

6.5 years 6 years 1.5 years

IND Submitted

NDA Submitted

NCATS RESEARCH PROGRAMS Components of Molecular Libraries Program Therapeutics for Rare and Neglected Diseases Office of Rare Diseases Research Bridging Interventional Development Gaps

(BrIDGs) Clinical and Translational Science Awards

(CTSA) FDA-NIH Regulatory Science Cures Acceleration Network

NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCINECES

NCATS STRUCTURE

Division of Pre-Clinical

InnovationChris Austin

Division of Clinical

Innovation Josie Briggs

(Acting)

Office of the Director

Tom Insel (Acting Director)

Kathy Hudson (Acting Deputy

Director)

Executive Office

Erin Shannon (Acting)

Office of Grants

Management & Review

Jane Steinberg (Acting)

Office of Policy, Communications,

& Strategic Alliances

Kathy Hudson (Acting)

Council CAN Board

Office of Rare Diseases Research

Steve Groft

NCATS UNIFIES THREE PROGRAM AREAS

Clinical and Translational Science Activities CTSAs Clinical Translational Science Awards

Rare Diseases Research and Therapeutics Office of Rare Diseases Research ORDR Therapeutics for Rare and Neglected Diseases

(TRND) Re-engineering Translational Sciences

NIH Chemical Genomics Center/Molecular Libraries program

Bridging Interventional Development Gaps BrIDGs Toxicology in the 21st Century

TRND PARTNERS

Academia Government Biopharmaceuticals

Patient Advocacy Groups

TRND Successful applicants don’t receive grants

Form joint project teams with TRND

Receive in kind support from TRND

scientists, laboratory and contract

resources

Goal is advancing compounds to FDA IND

clinical trials in humans

TRND PILOT PROJECTS, PROOF OF CONCEPT

Niemann- Pick C

Hereditary Inclusion Body Myopathy

Sickle cell anemia - IND received

Chronic Lymphocytic Leukemia IND

received

Shistosomiasis

TRND – 4 DRUG DEVELOPMENT PROJECTS APPROVED

Duchenne Muscular Dystrophy

Fragile X

Cryptococcal Meningitis

Core binding factor leukemia

LATEST TRND PROJECTS APPROVED

An inhibitor compound for Rx of fibrodysplasia ossificans Applicant is academic MD Compound shows efficacy in mouse model

Novel Rx for creatine transporter deficiency Applicant is a pharmaceutical Co. Mouse model show incr. brain metabolism and

cognative function Compount for Rx of neonatal herpes simplex

Applicant is academic pediatrician Compound can penetrate CNS, NIAID studied

LATEST TRND PROJECTS APPROVED

Deuterimum modified compound for shistosomiasis Applicant is pharmaceutical co. Enables lower and less frequent dosing

Drug candidate for Duchenne MD Applicant is pharmaceutical co. Drug is for a specific subgroup mutation

Rx for autoimmune pulmonary alveolar proteinosis Applicant is academic MD Developed as an inhaled Rx

TRND WILL FOLLOW MILESTONES AND TERMINATE PROJECTS – FOR INSTANCE

If no effect in animal models

Too much toxicity in preclinical testing

Poor bioavailability – can’t be absorbed

OTHER NCATS PROGRAMS

Cures Acceleration Network (CAN) Address challenges that impede translational

research Rescuing and Repurposing Drugs e.g.

lithium Designing a Tissue Chip for Drug Screening

With FDA and the Defense Advanced Research Projects Agency (DARPA)

“organ on a chip” Identifying and Validating Drug Targets

NCATS, ORDR AND ATAXIA RESEARCH

Many potential drug targets for new compounds heard at AIM 2012

High throughput screening at NCATS of thousands of molecules already being used by ataxia researchers

Rescuing and repurposing drugs is NCATS program and many examples given at AIM 2012

Programs at ORDR, NeuroNext, NCATS and TRND should offer HUGE opportunities for ataxia research ncats.nih.gov

NIH OFFICE OF RARE DISEASES RESEARCH - STAFF Steve Groft PharmD Ms. Mary Demory Dr. David Eckstein Ms. Marita Eddy (Angel Flight) Dr. John Ferguson Dr. Rashmi Gopal-Srivastava Mr. Christopher Griffin Ms. Henrietta Hyatt-Knorr Dr. Lata Nerurkar Ms. Susan Orr Lowe Ms. Geraldine Pollen Dr. Yaffa Rubinstein Dr. William Gahl (Clinical Director, NHGRI) Dr. P.J . Brooks (NIAAA)