The CFF Story: Innovating for a Cure, presented by Robert Beall, PhD, Cystic Fibrosis Foundation, HSG 2016

1. The CFF Story:
Innovating for a Cure
Huntington Study Group
November 4, 2016
Robert J. Beall, Ph.D.
Former President and CEO, Cystic Fibrosis Foundation

2. The CFF Story:
Innovating for a Cure
 Community
 Clinical Care
 Research
 Discovery & Development
 Treatment

3. Median Predicted Survival Age of US Patients
with Cystic Fibrosis
Source: Cystic Fibrosis Foundation, National Patient Registry
41
0
5
10
15
20
25
30
35
40
45
1940 1950 1960 1970 1980 1990 2000 2010 2015

4. 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
%ofCFindividualsovertheageof18
1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015
0
10%
20%
30%
40%
50%

5. 46%
Other Indications of Success
22%
CF Adults Employed
CF Adults Attending
College

7. Innovating
Community

8. Academics
• Research
• Care
• Training
Biopharmaceutical
• Translation
• Commercialization
CF Foundation
• Care
• Research
• Education
Ecosystem for Cystic Fibrosis Foundation Success
FDA
NIH

9. Innovating
Care

10. Care Center Network
Care Center Network
Peer accreditation
• 119 care centers,
• 107 adult programs,
• 51 affiliates

11. 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

12. 2002
50
60
70
80
90
100
110
20 25 30 35 40 45 50 55 60 65 70
FEV1PercentPredicted
BMI Percentile
FEV1 vs. BMI Percentile for Patients 6 to 17 Years, 2002 vs. 2012
32.2%17.5%
18.9%
2002 Median Values
31.5%

13. 2012
50
60
70
80
90
100
110
20 25 30 35 40 45 50 55 60 65 70
FEV1PercentPredicted
BMI Percentile
2012
FEV1 vs. BMI Percentile for Patients 6 to 17 Years, 2002 vs. 2012
13.4%
76.4%
4.5% 5.7%
2002 Median Values

14. CFF Recognized as Model

15. 2015 Annual Data Report

16. Patient Registry: Uses

17. Innovating
Research & Development

18. RDP Centers

19. Research Publications
0
500
1000
1500
2000
2500
New Publications 1,993

20. Working Hypothesis

21. Danny Then and Now

22. Cystic Fibrosis Transmembrane
Conductance Regulator
• Acts as a Chloride
Channel
• Controls Salt and
Water Balance in the
Airways

23. 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

24. TDP Process
Available
to
CF Patients
DISTRIBUTION
FDA
P
P
R
O
V
A
L
DEVELOPMENT
TDN
Bring Existing Drugs for
CF Indication
NDA
Clinical
Dosage
and
Efficacy
IND
Preclinical
Safety
Testing
Therapeutics
Development
Awards
DISCOVERY
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

25. Therapeutics Development Network

26. 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.

27. Venture Philanthropy in Action
High-throughput Screening

28. 2012 – FDA Approves Ivacaftor

29. Ivacaftor Improved FEV1
McKone, Borowitz….Davies et al, NACFC 2013. Poster 207
Ivacaftor vs
Placebo
Everyone on
Ivacaftor

30. Effect of Decreased Rate of Decline in FEV1
20
30
40
50
60
70
80
90
100
6 16 26 36 46 56 66 76 86
G551D With Ivacaftor
F508del/F508del

31. FDA Approves Lumacaftor/Ivacaftor
Combination for F508del Homozygotes

32. 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…

33. Innovating
For the Future

34. A Lifelong Cure For All CF Patients
Gene (DNA)
CF Mutation
Continuous
Therapy
Infection
Mucus
Inflammation
Nutrition….
RNA
Transcription
Daily
Therapy
CFTR modulation
Potentiators
Correctors
Symptoms
Lungs
liver
pancreas
gut
Protein
Translation
CFTR
Periodic
Therapy
Transcription
Translation (PTCs)
RNA replacement**
RNA editing
Replication
Permanent
Repair
Gene editing
Gene delivery
Stem cell biology

36. Innovating for the Future
February 2016

37. Dream Big
Continuously refine and replace existing therapies until
a safe, effective, permanent cure is available for all
individuals with CF.

38. Thank you.