The CFF Story:Innovating for a Cure

Huntington Study GroupNovember 4, 2016

Robert J. Beall, Ph.D.Former President and CEO, Cystic Fibrosis Foundation

The CFF Story:Innovating for a Cure

Community Clinical Care Research Discovery & Development Treatment

Median Predicted Survival Age of US Patients with Cystic Fibrosis

Med

ian

Pre

d. S

urvi

val A

ge

Source: Cystic Fibrosis Foundation, National Patient Registry

1940 1950 1960 1970 1980 1990 2000 2010 20150

5

10

15

20

25

30

35

40

45 41

As of 2015 There Are More Adults With CF Than Children With CF in the U.S.

Cystic Fibrosis Foundation. Patient Registry Annual Report. Bethesda, MD: Cystic Fibrosis Foundation.

2015

% o

f CF

indi

vidu

als

over

the

age

of 1

8

1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015

0

10%

20%

30%

40%

50%

46%

Other Indications of Success

22%

CF Adults Employed

CF Adults Attending College

InnovatingCommunity

Academics• Research• Care• Training

Biopharmaceutical• Translation• Commercialization

CF Foundation• Care• Research• Education

Ecosystem for Cystic Fibrosis Foundation Success

FDANIH

InnovatingCare

Care Center Network

Care Center Network

Peer accreditation• 119 care centers,

• 107 adult programs,

• 51 affiliates

Quality Improvement Program

• Web-based registry• Learning and Leadership Collaboratives• Leadership development • Benchmarking - identify and enable “best

practices”• Discipline-specific mentoring programs• Patient/family engagement and partnership• Transparency of center-level outcomes

2002

20 25 30 35 40 45 50 55 60 65 7050

60

70

80

90

100

110

BMI Percentile

FEV1

Per

cent

Pre

dict

ed

FEV1 vs. BMI Percentile for Patients 6 to 17 Years, 2002 vs. 2012

32.2%17.5%

18.9%

2002 Median Values

31.5%

2012

20 25 30 35 40 45 50 55 60 65 7050

60

70

80

90

100

110

2012

BMI Percentile

FEV1

Per

cent

Pre

dict

ed

FEV1 vs. BMI Percentile for Patients 6 to 17 Years, 2002 vs. 2012

13.4%

76.4%

4.5% 5.7%

2002 Median Values

CFF Recognized as Model

2015 Annual Data Report

Patient Registry: Uses

InnovatingResearch & Development

RDP Centers

Research Publications

20142013

20122011

20102009

20082007

20062005

20042003

20022001

20001999

19981997

19961995

19941993

19921991

19901989

19881987

19861985

19841983

19821981

0

500

1000

1500

2000

2500

New Publications 1,993

Working Hypothesis

Danny Then and Now

Cystic Fibrosis Transmembrane Conductance Regulator

• Acts as a Chloride Channel

• Controls Salt and Water Balance in the Airways

Therapeutics Development Program (TDP) Started in 1998

• Created to encourage industry and academia to focus on CF and CFTR as drug target

• Components of TDP

– Financial assistance

– Research tools and scientific advice

– Well organized clinical trial network

Venture Philanthropy

TDP Process

AvailabletoCF

Patients

DISTRIBUTION

FDAPPROVAL

DEVELOPMENT

TDN

Bring Existing Drugs for CF

Indication

NDAClinical

Dosageand

Efficacy

INDPreclinica

lSafetyTesting

TherapeuticsDevelopment

AwardsDISCOVERY

Basic Research• CFTR Corrector

Consortium• CFTR Structural

Consortium• Mucociliary

Clearance Consortium

High-throughput Screening

The CF Foundation has “really paved the way for other small disease nonprofits to take drug discovery into their own hands.” -Harvard Business School Professor Robert Higgins

Therapeutics Development Network

Highlights of CF TDN Studies (1998-2016)

• Network supports 25-35 studies annually:– 75% industry-based therapeutic trials– 25% PI-initiated

• Initial studies were early Phase (1 and 2)• Transition to larger Phase 3 trials

– First CFFT Phase 3 study in 2001– Industry moved to predominantly Phase 3 by

2009• PI initiated studies have focused on outcome

measure development • In total, over 150 studies involving thousands of

individuals with CF have been successfully completed.

Venture Philanthropy in Action

High-throughput Screening

2012 – FDA Approves Ivacaftor

Ivacaftor Improved FEV1

McKone, Borowitz….Davies et al, NACFC 2013. Poster 207

Impr

ovem

ent i

n Lu

ng F

unct

ion

(FE

V1

%)

Ivacaftor vs Placebo

Everyone on Ivacaftor

Effect of Decreased Rate of Decline in FEV1

6 16 26 36 46 56 66 76 8620

30

40

50

60

70

80

90

100

G551D With Ivacaftor

F508del/F508del

FDA Approves Lumacaftor/IvacaftorCombination for F508del Homozygotes

Venture Philanthropy: It is not just the money! It also involves access to:

• Expertise

• Patients

• Clinical Trial Network

• Data

• Specialized Resources

• Committed Community

Venture Philanthropy is not for the faint of heart…

InnovatingFor the Future

A Lifelong Cure For All CF Patients

Gene (DNA)

CF Mutation

ContinuousTherapyInfectionMucusInflammationNutrition….

RNA

Transcription

DailyTherapy CFTR modulationPotentiatorsCorrectors

Symptoms

Lungs

liver

pancreas

gut

Protein

Translation

CFTR

PeriodicTherapy TranscriptionTranslation (PTCs)RNA replacement**RNA editing

Replication

PermanentRepair Gene editingGene deliveryStem cell biology

Innovating for the Future

February 2016

Dream Big

Continuously refine and replace existing therapies until a safe, effective, permanent cure is available for all

individuals with CF.

Thank you.