Andrea Baruchin, Ph.D.Senior Advisor to the President

India-US Technology SummitNovember 19, 2014

Purpose Created by Congress:→ To support the NIH in its mission; → To advance collaboration with biomedical researchers from universities,

industry and not-for-profit organizations.

Structure• 501(c)(3) not-for-profit organization;• Independent Board of Directors;• NIH Director and FDA Commissioner ex-officio Board Members

Highlights• Raised over $800 million since 1996;• Supported over 500 projects;

• research partnerships • scientific education/training• conferences/events • capital programs

Building partnerships for discovery and innovation to improve health.

Our role…

Identify:• Important scientific problem• Key players• Resources required and sources of

support• Neutral convener; trusted party to

provide safe harbor for discussions

Establish:• Highest level of ethical standards• Clear goals and milestones• Effective mechanism to generate

scientific consensus• Nimble infrastructure and project

expert project management

Facilitate: • Discussions with key opinion leaders

and regulatory decision makers• Integrated approach to cross-sector

partnerships• Communications; ensure all partners’

voices are heard;

Enable: • Sharing of data and expertise to

collaboratively address medical needs

• Resource mobilization• Manage grants, contracts, and

projects; oversee and conduct research

What we do, how we do it…

Lessons Learned

• A matrix that is greater than the sum of its parts;

• Well defined objectives, budgets, milestones and deliverables;

• Common governance, rules and legal framework;

• Realistic funding goals, expectations and timelines;

• Projects aligned with donor interest;

• Appreciation of the value of gifts;

• Collaboration adds complexity: must “play nice with others!”;

• Nimble, transparent and accountable.

Partnership “must-haves”

How we Fund Our Programs

Industry

Government

Associations Foundations

Individuals

FNIH has no endowment

Funding History

$808 million

Our history of support for hundreds of projects since 1996 offers many models for partnerships between the public and the private sectors, ranging from simple fund transfers to highly complex and interactive programs.

TrainingEventsCapitalResearchAgencyFamily FundsUnrestrictedNIH Contribution

$816 M

Support for over 500 projects

Funding & Partnership Models

FNIH

NIH

Private Sector Funders

Intramural or Extramural

Lab

$$ Flow

FNIH

NIH

Private Partners

$$ Flow

Scientific Interaction

Intramural or Extramural

Lab

FNIHSteering

Committee/Project Team

Model 1 Model 2

Scientific Programs &

Research

(and/or)

Select Programs“When you’ve seen one partnership…you’ve seen one partnership.”

• Public-private partnership with NIH, 10 companies, non-profits.

• Aims to distinguish targets of disease most likely to respond to new therapies in:

• Alzheimer’s Disease;• Type 2 Diabetes;• RA/SLE.

• Partners have developed research plans; are sharing costs, expertise, resources.

• Launched in 2014, $230M investment over five years on pilot projects.

• FNIH acts as a neutral convener, secures the funding and scientific expertise, establishes partnership governance and provides program and project management for AMP.

Accelerating Medicines Partnership (AMP)

Industry members

Government members

Non-profit members

AMP Participants

• Qualifies biomarkers for specific applications in diagnosing disease, predicting therapeutic response, and improving clinical practice.

• Generates information useful to inform regulatory decision-making.

• Employs rigorous, inclusive governance and project management with clearly defined goals and milestones.

• Addresses a broad range of disease / therapeutic areas – cancer, neuroscience, metabolic disorders, immunity & inflammation.

• Pre-competitive; makes consortium project results broadly available to the entire scientific community.

Our Founding Partners: FDA, NIH, FNIH, PhRMA, BIO, CMS

Fosters the exchange of knowledge and expertise among industry, academic, and government leaders

Biomarkers Consortium

Alliance

ECOG-Acrin

NRGNCI-C

SWOGNational Clinical Trials

Network

S1400Master Protocol

Thank You !

Developing effective new medicines takes too long, costs too much and fails too often.

AMP

Success

Efficacy Failures

Other Failures

Success

Other Failures

Current targets Animal models Cell lines

AMP targets Emerging Technologies

• DNA sequencing• Proteomics• Single-cell analysis• Bioengineered cells• Imaging

Extensive Human Data• Tissue/blood samples• Clinical information• Demographics

Big Data Tools

Efficacy Failures

Lack of efficacy currently accounts for more than half of all drug failures in Phase II clinical studies

AMP’s target validation efforts aimed at improving efficacy and increasing success rate

Efficacy

AMP Governance & Membership

Alzheimer's diseaseSteering Committee

FNIH program management

Extended Executive Committee Core Executive Committee

Members•Francis Cuss, BMS

•Richard Hodes, NIA•Kathy Hudson, NIH•Tom Insel, NIMH

Co-chairs• Mike Decker, AbbVie• Neil Buckholtz, NIA

EC Liaison• Richard Hodes, NIA

Members• Maria Carrillo, ALZ• Xiaoming Guan, GSK• Tim Harris, Biogen Idec• Walter Koroshetz, NINDS• Nick Kozauer, FDA• Mark Mintun, Lilly • Pat Walicke, NINDS

Type 2 DiabetesSteering Committee

Co-chairs• Andy Plump, Sanofi• Phil Smith, NIDDK

EC Liaison• Griffin Rodgers, NIDDK

Members• Keith Demarest, J&J• Joe Hedrick, J&J• Dermot Reilly, Merck• Hartmut Ruetten, Sanofi• Melissa Thomas, Lilly• Jeff Pfefferkorn, Pfizer• Liangsu Wang, Merck• Dan Rader, UPENN

RA, SLE & related diseasesSteering Committee

Co-chairs• Marty Hodge, Pfizer• Bob Carter, NIAMS

EC Liaison• Bob Carter, NIAMS

Members• Christopher Arendt, Sanofi• Beth Axtell, Arthritis Foundation• Carolyn Cuff, AbbVie• Ellen Goldmuntz, NIAID• Satwant Narula, BMS• Lisa Olson, AbbVie• Dan Rotrosen, NIAID• Susana Serrate-Sztein, NIAMS• Jonathan Zalevsky, Takeda• Dennis Zaller, Merck• Jeff Browning, ALR/RFI

• Bill Chin, PhRMA• Bill Hait, J&J• Jim Sullivan, AbbVie• Patrick Vallance, GSK• Rupert Vessey, Merck

• Doug Williams, Biogen Idec• Janet Woodcock, FDA• Tachi Yamada, Takeda• Elias Zerhouni, Sanofi

•Steve Katz, NIAMS•Rick Lifton, YALE•Jan Lundberg, Lilly•Griffin Rodgers,

NIDDK

Co-chairs•Francis Collins, NIH

•Mikael Dolsten,

Pfizer • Steve Hoffmann, FNIH• Maria Vassileva, FNIH• David Wholley, FNIH

AMP – Research Topics

Disease area Research plan topics Deliverables and approach

Alzheimer's disease

Exploratory biomarker validation in clinical trials and network analysis on human tissue

• Embed (ie, incentivize the use of) exploratory biomarkers in NIH-funded clinical trials to develop biomarkers of disease progression and surrogate endpoints

• Conduct network analysis in human brain samples to identify genetic nodes & networks linked to AD to support target identification & validation

Type 2 DiabetesSequencing & phenotyping of targets of interest and a tool to enable easy interrogation of all available data

• Create a knowledge portal containing comprehensive T2DM (& diabetic complications) genotype/phenotype data sets – apply informatics to identify predictors of risk and potential drug targets

• Conduct targeted sequencing/genotyping of high priority targets of interest (as defined by industry

RA, SLE & related autoimmune

diseases

Immune module deconstruction with blood/tissue and cross-disease comparisons

• Conduct extensive profiling of key immune modules in highly refined subsets of relevant cells in informative cohorts to establish pathway/network maps of RA & SLE; high priority targets identified from pathway analysis to be validated via RNAi. The data will be made available in a knowledge portal

- Informative cohorts include: Early RA, Established RA (responder/non-responder), Lupus Nephritis, Skin Lupus

Funding for AMP projects are split 50/50 between industry participants and NIH

AMP – Budget

($Millions) Total Project Total NIH Total Industry

Alzheimer’s Disease 129.5 67.6 61.9

Type 2 Diabetes 58.4 30.4 28

Rheumatoid Arthritis & Lupus 41.6 20.9 20.7

Total 229.5 118.9 110.6

AMP – IP & Data Sharing

• Research supported by AMP will be precompetitive

• All data will be shared broadly

• AMP supported research will not be patented

Biomarkers ConsortiumContributing Partners

For-Profit CompaniesActelionAmgenAstraZenecaCrescendo BioscienceDaiichi Sankyo, IncEisai, IncJohnson & JohnsonEli Lilly & CompanyLundbeckMerck Sharpe & Dohme Corp.MetabolonMitsubishi Tanabe Pharma America, IncMyriad RBMPfizer, IncRegeneron Pharmaceuticals, Inc.SanofiTakeda Pharmaceuticals USA, Inc

Non-Profit OrganizationsAlzheimer’s AssociationAmerican Diabetes AssociationAmerican Orthopaedic Society for Sports MedicineArthritis FoundationAutism SpeaksBiotechnology Industry OrganizationCalifornia Dairy Research Foundation (CDRF)Centre for Proteomic and Genomic ResearchCHDI FoundationDairy Research InstituteFoundation for Health Improvement and TechnologyJuvenile Diabetes Research FoundationPharmaceutical Research and Manufacturers of AmericaPROOF Centre of ExcellenceRadiological Society of North AmericaUS Pharmacopeia

Biomarkers ConsortiumGovernance Structure

Executive CommitteeNIH / FDA / CMS / industry / FNIH

Inflammation & Immunity

Steering Committee

NeuroscienceSteering Committee

Metabolic Disorders

Steering Committee

CancerSteering

Committee

Multiple Project TeamsRepresentatives from NIH, FDA, Industry, Subject experts from academia

Biomarkers ConsortiumLaunched Projects

Neuroscience PET Radioligand in Neuroinflammation Alzheimer’s Plasma Proteomics Alzheimer’s CSF Proteomics* Alzheimer’s / MCI Placebo Data Analysis*

Executive Committee■ Kidney Safety Biomarkers■ Skin Infection Pneumonia

(CABP/ABSSSI)■ Hospital-Acquired & Ventilator Acquired

Bacterial Pneumonia

Cancer• FDG-PET in Lung Cancer• FDG-PET in Lymphoma I-SPY 2 Trial** Minimal Residual Disease in ALL

Inflammation and Immunity■ Osteoarthritis Biomarkers

Metabolic Disorders Adiponectin Carotid MRI Reproducibility Sarcopenia Consensus Definition■ Atherosclerosis In-Silico Modeling■ Beta Cell Clinical Studies■ Bone Quality

■ Ongoing Projects Completed Projects * Final publication pending ** Transitioned to standing trial

Biomarkers ConsortiumAccomplishments

16 Total projects launched

8 Projects completed

3 New projects recently approved

3 FDA guidances completed with BC contributions

4 Drugs advanced toward approval with support from BC projects

20+ Journal articles published and mentioned in 50 others

• Multi-arm Master Protocol

• Homogeneous patient populations & consistent eligibility from arm to arm;

• Each arm independent of the others;

• Infrastructure facilitates opening new arms faster;

• Phase II-III design allows rapid drug/biomarker testing for detection of “large effects.”

• Screening large numbers of patients for multiple targets by a broad-based NGS platform reduces the screen failure rate.

• Provides a sufficient “hit rate” to engage patients & physicians.

• Bring safe & effective drugs to patients faster.

• Designed to facilitate FDA approval of new drugs.

Rationale for Lung-MAP Protocol

Lung-MAP Protocol

S1400DFGFR

FGFR ampl, mut, fusion

S1400CCDK4/6

Cell cycle gene alteration

S1400EHGF

C-MET Expr

S1400BP13K

PIK3CA mut

S1400ANon-match(Anti-PD-L1)

Arm1 Arm2

1:1

Arm1 Arm2

1:1

Arm1 Arm2

1:1

Arm1 Arm2

1:1

Arm1 Arm2

1:1

1 1 Medi47362 2 DocetaxelMedimmune

1 GDC-00322 DocetaxelGenentech

1 1 Palbociclib2 2 Docetaxel

Pfizer

1 AZD45472 DocetaxelAstrazeneca

1 1Rilotumumab+ erlotinib

2 2ErlotinibAmgen

Alzheimer’s Disease Neuroimaging Initiative (ADNI)

• Natural history study of normal cognitive aging, mild cognitive impairment (MCI) and early Alzheimer’s disease (AD).

• Launched in 2004 at over 50 clinical sites in the US and Canada.• Designed to develop methods, acquire data, and form a collaborative network of clinical and

imaging sites to facilitate the utilization and evaluation of neuroimaging and other biomarkers for use in clinical trials aimed at slowing the onset and progression of Alzheimer’s disease.

• Public-private partnership, funded through the NIH ($100M) and the private sector, ($40M) coordinated by the Foundation for the NIH

• World-wide network to improve AD studies and clinical trails for disease-modifying treatments

• Optimize and standardize biomarker methods for early detection and disease progression.• Validate biomarkers for use in clinical trials:

– As measures of change– As diagnostics or predictors (symptomatic and re-symptomatic)

• ADNI 3 planning now underway

About ADNI

• Largest public-private partnership on AD for industry leaders to work together in a proven, pre-competitive environment:– Cost sharing and cost savings;– High level interactions with top clinical/biomarker AD investigators;– Idea and data sharing not possible in competitive environment;– Interaction with FDA – ongoing guidance on endpoints and validation.

• Study design and objectives address industry needs:– Standardization of all methods for regulatory approval;– Identification of patients at risk in the pre-dementia stage;– Validation of biomarkers to measure change and treatment effects;– Validation of biomarkers to identify early AD pathology;– Longitudinal data with biomarkers for design and powering of trials;

• ADNI plays a major role in:– Providing new information concerning the pathophysiology of AD;– Developing early detection methods and improved treatment trials;– Determining diagnostic requirements;– Providing tools for evaluating milder patients;– Understanding disease progression/rate of change during different stages of

disease.

Current ADNI 2 PPSB Partners

Board of Directors

• Charles Sanders, MD – ret. GSK• Mrs. William McCormick Blair – Lasker

(Emeritus)• Kathy Bloomgarden, PhD – Ruder Finn• Mrs. William Cafritz – Kennedy Center• James Donovan – Goldman Sachs• Joseph Feczko, MD – retired Pfizer• Maria Freire, PhD – FNIH • Miles Gilburne – ZG Ventures• Paul Herrling, PhD – Novartis• Ronald Krall, MD – ret. GSK• Sherry Lansing – Sherry Lansing Foundation• Freda Lewis-Hall, MD – Pfizer• Edison Liu, MD, PhD – Jackson Labs• Ann Lurie – Lurie Investments, Inc.

• Joel Marcus – Alexandria Real Estate Equities• Steven Mayer – ret. Human Genome Sciences

& CoGenesys• Paul Montrone, PhD – Perspecta Trust• Martin Murphy, PhD – AlphaMed Consult• Garry Neil, MD – retired Johnson and Johnson • Steven Paul, MD – Weill Cornell Med College• Hon. John Porter – Hogan Lovells• Mrs. Jillian Sackler, DBE – AMS Found• Mrs. Lily Safra – Safra Foundation• Ellen Sigal, PhD – Friends of Cancer Research• Solomon Snyder, MD – Johns Hopkins• Nina Solarz - philanthropist• Samuel Thier, MD – Harvard Medical School• Anne Wojcicki – 23andMe

NIH Director/FDA Commissioner ex-officio Board members