Thomas R. Insel, M.D., Acting Director

IOM Forum on Drug Discovery, Development, and Translation

June 4, 2012

Associated Press, May 21, 2003: “Democratic

presidential candidate Joe Lieberman on Wednesday

called for a $150 billion, 10-year federal initiative to

quickly bring cures for diseases to the marketplace. . . “

S.2104, the American Center for Cures Act of 2005 (introduced 12/14/2005) Stand alone bill for a Center within NIH; authorization of

$5,000,000,000

S.2988, the Accelerating Cures Act of 2008 (introduced 5/7/2008)

Biotechs Starved by Financial Collapse

Different Set of Reviewers (i.e. VC and Patients)

Broaden Eligible Grantees

“X Prize” Follow-on to ARRA

“DARPA-like Authorities” (Sen. Stevens [R-AK])

Specter Bill Would:

create an entity outside the NIH

authorize use of interagency agreements with the Center

for Scientific Review performing peer review

prescribe the expertise necessary for members of the initial

review groups

manage the program by a high level Board

increase the authorization for NIH to $40B

authorize $1 billion in FY10-11

Established in NIH Office of the Director

Authorized budget for FY 2010: $500 M Specifically appropriated “new money”

Creates New Award Mechanisms Cures Acceleration Partnership Awards: up to $15 M,

requiring matching funds ($1 for every $3 awarded by NIH) Cures Acceleration Grants: $15 M per award Cures Acceleration Flexible Research Awards: DARPA-like

research authority, up to 20 percent of CAN

CAN Review Board 24 member advisory board; Patient Advocates, VC Advise NIH Director about barriers to successful translation

of basic science into clinical applications

April 16, 2010

Honorable Tom Harkin

Chairman

Subcommittee on Labor-HHS-Education

Committee on Appropriations

United States Senate

Washington, DC 20510

Honorable Thad Cochran

Ranking Member

Subcommittee on Labor-HHS-Education

Committee on Appropriations

United States Senate

Washington, DC 20510

Dear Chairman Harkin and Ranking Member Cochran:

We respectfully request that the Senate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies include funding for the newly-enacted Cures Acceleration Network in the Fiscal Year (FY) 2011 Labor-HHS appropriations bill.

Abigail Alliance for Better Access to Developmental Drugs

AIDS Institute

Alexion Pharmaceuticals

Alliance for Aging Research

Alliance for Regenerative Medicine

Alpha-1 Association

Alpha-1 Foundation

ALS Association

ALS Therapy Development Institute

Alseres

Alzheimer's Association

American Institute for Medical and Biological Engineering

American Parkinson Disease Association

Association for Clinical Research Training

Association for Patient-Oriented Research

Association of Academic Health Science Libraries

AVAC: Global Advocacy for HIV Prevention

Batten Disease Support and Research Association

Benign Essential Blepharospasm Research Foundation

BIO Ventures for Global Health

Biotechnology Industry Organization

Californians4cures

CANN - Community Access National Network

Celiac Disease Center at Columbia University

Ceregene

Citizens United for Research in Epilepsy

Clinical Research Forum

Coalition of Heritable Disorders of Connective Tissue

Colon Cancer Alliance

COPD Foundation

Council for American Medical Innovation

Cutaneous Lymphoma Foundation

Cystic Fibrosis Foundation

Digestive Disease National Coalition

Dystonia Advocacy Network

Dystonia Medical Research Foundation

Easter Seals

FasterCures

Foundation for Sarcoidosis Research

Friends of Cancer Research

Genetic Alliance

Global Healthy Living Foundation Harlem United Community AIDS Center, Inc Huntington’s Disease Society of America Infectious Diseases Society of America International AIDS Vaccine Initiative International Foundation for Functional Gastrointestinal Disorders International Myeloma Foundation Interstitial Cystitis Association Juvenile Diabetes Research Foundation Kakkis EveryLife Foundation Leukemia & Lymphoma Society Lung Cancer Alliance Medical Library Association Michael J. Fox Foundation for Parkinson's Research Muscular Dystrophy

Association National Disease Research Interchange National Health Council National Minority AIDS Council National MPS Society National Multiple Sclerosis Society National Parkinson Foundation National PKU Alliance National Tay-Sachs & Allied Diseases Association National Venture Capital Association NephCure Foundation New York Stem Cell Foundation Parent Project Muscular Dystrophy Parkinson Alliance and Parkinson’s Unity Walk Parkinson's Action Network Parkinson's Disease Foundation PKD Foundation PXE International Rett Syndrome Research Trust Scleroderma Foundation Society for Clinical and Translational Science Spinal Muscular Atrophy Foundation SRI International Student Society for Stem Cell Research The Christopher and Dana Reeve Foundation Tuberous Sclerosis Alliance

Malcolm Gladwell, Annals of Innovation, “The Treatment,”

The New Yorker, May 17, 2010, p. 69

ABSTRACT: ANNALS OF INNOVATION about the process of developing cancer drugs. In the world of cancer research, there is something called a Kaplan-Meier curve, which tracks the survival of patients in the trial of an experimental drug. In its simplest form, it consists of two lines. The first follows the patients in the “control arm,” the second the patients in the “treatment arm.” In most cases, those two lines are virtually identical. But every now and again the patients in the treatment arm will live longer than the patients in the control arm, and the two lines on the Kaplan-Meier will diverge. Tells about Safi Bahcall, the C.E.O. of Synta Pharmaceuticals, a small biotechnology company located outside Boston. In the summer of 2006, Synta had two compounds in development. One was a cancer drug called elesclomol. The other was an immune modulator called apilimod. Phase 2 testing of elesclomol resulted in surprising data indicating that the compound might be an effective treatment for metastatic melanoma, a form of skin cancer that was notoriously resistant to treatment. Describes Emil Freireich's research into drugs to treat acute lymphoblastic leukemia (ALL) in the nineteen-fifties and sixties. Working with a group that included Tom Frei, of the National Cancer Institute, and James Holland, of the Roswell Park Cancer Institute, Freireich started treating ALL patients with a combination of drugs. They discovered that they didn't need a magic bullet—a superdrug that could stop all cancer in its tracks. A drug that worked a little bit could be combined with another that worked a little bit and another that worked a little bit, and the combination could turn out to be spectacular. Tells about Bahcall's partner, a cell biologist named Lan Bo Chen. Drug hunters like Chen fall into one of two broad schools: “rational design,” in which the scientist starts with the disease and works backward, or “mass screening,” in which a scientist begins with a drug candidate and searches for diseases it might attack. Chen belonged to the latter school. Describes the drug-screening process Chen went through to discover elesclomol. Discusses the complexities of drug testing: there are a variety of ways in which a drug can be applied and therefore, a variety of ways in which it can be tested against a variety of different cancers in different stages. Tells about the Phase 2 trial that produced the encouraging elesclomol results for melanoma.

From 1996 to 1999 The U.S. food

and Drug Administration approved 157

new drugs. In the comparable period a

decade later—that is, from 2006 to

2009—the agency approved 74. Not

among them were any cures, or even

meaningfully effective treatments, for

Alzheimer's disease, lung or

pancreatic cancer, Parkinson's

disease, Huntington's disease, or a

host of other afflictions that destroy

lives.

Breakthroughs and Breakdown

Drugs that changed lives, for better or

worse

Desperately Seeking Cures How the road from promising scientific breakthrough to real-world remedy has become all but a dead end.

By Sharon Begley and Mary Carmichael |

NEWSWEEK

Published May 14, 2010

From the magazine issue dated May 31, 2010

In a first-of-a-kind collaboration between academia and industry,

Pfizer Inc. will give scientists at Washington University School of

Medicine in St. Louis unprecedented access to information regarding

more than 500 pharmaceuticals and pharmaceutical candidates in a

partnership that focuses on discovering new uses for existing

compounds.

Under the five-year, $22.5 million agreement announced Monday,

May 17, Pfizer will provide access for Washington University

scientists to view extensive research data on a large array of Pfizer

pharmaceutical candidates that are or were in clinical testing.

Washington University, Pfizer announce groundbreaking

research collaboration

As part of an innovative collaboration, scientists with Pfizer

Inc.'s Indications Discovery Unit are moving to the Center of

Research Technology and Entrepreneurial Expertise

(CORTEX-pictured above), adjacent to Washington

University School of Medicine.

May 17, 2010 By: Caroline Arbanas

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.”

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Disorders with Known Molecular Basis

Source: Online Mendelian Inheritance in Man, Morbid Anatomy of the Human Genome

250 with

therapy

Past decade: 17-36 NMEs/year

Drug Discovery

10,000 Compound

s

1 Approve

d

Drug

Preclinical

Testing Clinical Trials FDA

Review Clinic

1.5

Years

6 Years 6.5 Years

250

Compounds

5

Compounds

82% fail in Phase II

Basic Laboratory

Research

Translational

Research Population

Research

Clinical

Research

Improved

Public

Health

Standard Model The Way it Should Work

Basic Laboratory

Research

Patient-oriented

Clinical Research

Population-based Clinical

Research Clinical Trials

Improved

Public Health

Clinical and Translational Science Activities

Clinical and Translational Science Awards

Rare Diseases Research and Therapeutics

Therapeutics for Rare and Neglected Diseases

Office of Rare Diseases Research

Re-engineering Translational Sciences

Tox-21 and Tissue Chip Programs

Repurposing

New Therapeutic Uses for Existing Drugs

Cures Acceleration Network (CAN)

CTSA Other

SBIR/STTR CAN

ORDR TRND

Clinical and Translational Science Awards (CTSAs)

Support a national consortium of medical research institutions

Work together to improve the way clinical and translational research is conducted nationwide

Aim to accelerate the research translation process

Therapeutics for Rare and Neglected

Diseased (TRND) Program

Designed to re-engineer the development of new drugs for

rare and neglected diseases

Specifically intended to stimulate research collaborations for

drug discovery and development between NIH and:

Academic scientists

Nonprofit organizations

Pharmaceutical and biotechnology companies

Tox21: Toxicology in the 21st Century

A collaboration with:

NIH’s National Institute of Environmental Health Sciences

U.S. Environmental Protection Agency

U.S. Food and Drug Administration

Designed to screen a collection of 10,000 compounds composed of environmental chemicals and drugs approved for use

Looks for compounds’ potential to disrupt biological pathways that may be toxic

Tissue Chip for Drug Screening: NIH‒FDA‒DARPA

Collaboration

Aims to develop a tissue chip that mimics human

physiology to screen for safe, effective drugs

Liver, heart, lung, other cell types

Designed for multiple types of readouts

NIH and Defense Advanced Research Projects Agency

(DARPA) contribute $70M over 5 years; FDA provides

guidance

Seeking best ideas in engineering, biology, toxicology

Clinical and Translational Science Activities

Clinical and Translational Science Awards

Rare Diseases Research and Therapeutics

Therapeutics for Rare and Neglected Diseases

Office of Rare Diseases Research

Re-engineering Translational Sciences

Tox-21 and Tissue Chip Programs

Repurposing

New Therapeutic Uses for Existing Drugs

Cures Acceleration Network (CAN)

Created to advance development of “high need cures”

Reduces barriers to translation in areas the private

sector is less likely to pursue

Funded via:

Grant awards with or without partnership

Flexible Research Awards: DARPA-like authority

Not to exceed 20 percent of total appropriated funds

per fiscal year

FY 2012 budget: $10 million (FY 2013 PB: $50 million)

24 members appointed by Secretary DHHS

At least one member eminent in the following areas:

basic research, medicine, biopharmaceuticals, discovery

and delivery of medical products, bioinformatics and

gene therapy, medical instrumentation, regulatory review

and approval

At least 4 members recognized as leaders in venture

capital or private equity investing

At least 8 individuals representing disease advocacy

organizations

“$10M for CAN Board and related activities”

CAN Board encouraged to create measurable

outcomes to track success

IOM workgroup “to review, evaluate, and identify

issues related to CAN authority” and report to CAN

Board to help it identify ways to accelerate cures

IOM should include NIH, FDA, AHRQ, CDC, PTO

Patent authority, marketability, use of high

throughput analysis, regulatory timelines, and cost

structure issues related to CAN

How will CAN have greatest impact?

What tools, methods, and approaches can accelerate translational science? (FDA, CDC, AHRQ)

Best use of CAN matching and flexible research authorities? (DARPA, DTRA, BARDA)

How will CAN assist public-private partnerships? (Pharma, Biotech, VC, advocacy)

How will CAN interact with regulatory science initiative? (FDA)