Our world-class team monitors developments in Parkinson’s research, identifying top priorities for the field. We work closely with the Parkinson’s community to initiate, fund, and lead high-impact projects and collaborations. Presentation from a Research Roundtable held in New York on November 12, 2011.

1. MJFF’s Purpose, Promise and Plan for
Speeding New Parkinson’s
Treatments to Patients
Research Roundtable
New York, New York
November 12, 2011

2. Today’s Agenda
 MJFF Overview
Deborah W. Brooks
The Michael J. Fox Foundation for Parkinson’s Research
 MJFF Research Progress & Remaining Challenges
Todd Sherer, PhD
The Michael J. Fox Foundation for Parkinson’s Research
 Panelists
Anders Björklund, MD, PhD
Lund University
John Dunlop, PhD
Pfizer, Inc., Neuroscience Research Unit
Mark Frasier, PhD
The Michael J. Fox Foundation for Parkinson’s Research
 Questions & Answers Session
2

3. MJFF Overview
Deborah W. Brooks
Co-Founder & Executive Vice Chairman
The Michael J. Fox Foundation for Parkinson’s Research
3

4. Why we exist…
Drive the Best Parkinson’s Research
Deliver Improved Therapies and a Cure
Our world-class team monitors developments in Parkinson’s
research, identifying top priorities for the field. We work closely with
the Parkinson’s community to initiate, fund, and lead
high-impact projects and collaborations.
4

5. With over $270M funded since 2000, we are on a mission to speed a cure
 In 2010, we received nearly 65,000 contributions—substantially all from individuals
who have a stake in our success. And, our movement is building.
 We promise impact, efficiency and accountability: over 87 cents of every $1 spent
goes straight to research program efforts. We deploy donations conscientiously,
with wisdom and integrity. We deliberately have no endowment or excess reserves.
 Our in-house staff of 7 PhDs, 1 MD and 7 business strategists tap the advice of
experts from academia and industry globally. We have an informed opinion and
share it passionately.
60
new commitments
50
40
in millions
30
20
10
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
(est.)
5

6. Drug development is long, costly and risky…but can be smarter
Therapeutic
Target Development Pre-Clinical Clinical Regulatory
Discovery Testing
Validation & Testing Approval
Optimization I II III
Basic Discovery Preclinical Clinical
Understanding disease Convert biology into therapies Determine safety and efficacy
mechanisms Partly done in academic and in patients
Mostly done by academics biotech laboratories Mostly done by large pharma
$156 million/year $680 million/year
MJFF steps in to drive translation and
assure that promising therapies get
closer to patients
6

7. 2011 MJFF Research Progress
and
Remaining Challenges
Altering Disease: Disease Modifying Therapies
LRRK2: A Collaborative Example
Repositioning Drugs
Improving Symptomatic Treatments
Targeting Serotonin Receptors
Todd Sherer, PhD
Chief Executive Officer
The Michael J. Fox Foundation for Parkinson’s Research
7

8. There are numerous therapeutic needs for PD patients
Treat Symptoms
Alter Disease
& Side Effects
Validate
Genetic Dyskinesias
Targets
Develop
Non-Motor
Trophic
Symptoms
Factors
8

9. Multiple approaches to altering the course of PD
MJFF has committed nearly $115M to advance
disease modifying therapies
Cause of PD Restoration of Dopamine Biological Pathways
 Alpha-Synuclein: Genetic  Trophic Factors: Data  Inflammation: Inhibiting
association in familial cases continues to show promise inflammation could slow the
of PD; pathology evidence that increasing the levels of progression of PD
trophic factors can protect
 LRRK2: Protein kinase brain cells in PD  Oxidative Stress:
function makes LRRK2 a Decreasing oxidative stress
highly druggable target can protect dopamine
neurons
9

10. MJFF LRRK2 efforts are driving research towards the clinic
MJFF focuses on four key areas within LRRK2 research, reducing
research redundancies and facilitating collaborations among investigators
– over $38M spent on LRRK to date
Improve
Develop
understanding
LRRK2
of LRRK 2
research tools
biology
Supports
Study LRRK2
LRRK2
impact
therapeutic
clinically
development
10

11. LRRK2 Biology Consortium – A Collaborative Example
MJFF has established the LRRK2 biology consortium across 20 research labs
throughout the world. The consortium is designed to promote real time data
sharing, open discussion and distribution of tools among consortium members.
Mechanisms
• Agree to share for sharing • Prototype
data and tools compound
• Overlapping shared with 18
• Website – teams
approaches
protocols and • Novel
data collaborative
• Monthly calls projects
and annual developed
Over 20 sites summit meeting between teams
worldwide
Tangible
interactions
11

12. Expert Insight: John Dunlop, PhD
LRRK2 Consortium: How collaborative science is
accelerating drug development
John Dunlop, PhD
Chief Operating Officer
Neuroscience Research Unit
Pfizer
12

13. Repositioning compounds may lead to disease altering therapies
Drug repositioning aims to test therapies already clinically available for
effectiveness in PD
GOAL: Mitigate the time and costs involved in finding new therapies for PD
Traditional drug development pipeline
Phase I Phase I
Preclinical Phase II/III Regulatory
safety in safety in
Studies efficacy Approval
controls PD patients
Acceleration by repositioning drugs that are deemed “safe” therapies
Phase I Phase I
Preclinical Phase II/III Regulatory
safety in safety in
Studies efficacy Approval
controls PD patients
13

14. Expert Insight, Mark Frasier, PhD
Repositioning Pioglitazone: From Diabetes to PD
Mark Frasier, PhD
Director, Research Programs
The Michael J. Fox Foundation for Parkinson’s Research
14

15. Repurposed drug made ready for significant NIH support
Pioglitazone as a disease-modifying therapy
Therapeutic
Target Development Pre-Clinical Clinical Regulatory
Discovery Testing
Validation & Testing Approval
Optimization I II III
MJFF brokers introduction to clinicians
2004 Grant: Pre-clinical testing
2007 Grant: Dosing and Bioavailability
Available compound ID
2010: NIH funded clinical trial
2010: MJFF supports biomarker add on
15

16. Multiple promising trials and approaches are taking place
Novel Drug Targets
 Hypothesis for use of trophic factors to treat PD
remains viable and exciting
Trophic Factors/Ceregene  Pre-clinical and early phase clinical results
continue to show promise
 Attempts to remove alpha-synuclein protein
aggregates
AFFITOPE PD01  First time a vaccine approach has been tested
in the clinic for PD
Repositioned Compounds
 Calcium channel blocker for hypertension
Isradipine  Found to be neuroprotective in pre-clinical
models of PD
 Increasing urate levels could both lower the risk
Inosine of getting PD and slow the progression of the
disease
 Smoking linked to decreased risk of PD
Nicotine  First test as a disease-modifying therapy in PD
16

17. Clear need to develop treatments for motor & non-motor symptoms
MJFF has funded over $40M in research towards developing treatments
for both treating dyskinesia and non-motor symptoms.
 Includes cognitive dysfunction, anxiety, memory
Non-Motor loss and mood disorders
Symptoms  Relieving these symptoms would lead to a better
quality of life for those living with PD
 Uncontrolled body movements that result from
dopamine-replacement therapy
Dyskinesia
 Breakthroughs in treating dyskinesia would expand
options for treating PD
17

18. Funding two parallel tracks for improving symptomatic treatments
MJFF continues to invest in developing new therapies as well as determining how
to best assess these therapies in the clinic
Efforts include: Rationale – Why prioritize?
 Shown to reduce levodopa induced dyskinesia
in pre-clinical studies
mGluR5  Addex Pharmaceuticals and Novartis are
conducting trials to test mGluR5 antagonists in
PD patients
 New methods of delivering levodopa that will
L-Dopa Delivery result in constant blood levels compared to
“peaks and valleys” currently experienced
 Non-dopamine gene therapy strategy in
development
Neurologix  Designed to normalize brain physiology and
reduce the symptoms of PD
 Repurposing droxidopa (orthostatic
Droxidopa hypotension) in an effort to see if it can abate
gait, sleep and cognitive disorders in PD
 Targeting serotonin receptors could be key in
Serotonin Receptors reducing dyskinesia
18

19. Expert Insight: Anders Björklund, MD, PhD
Advancing Treatments for Dyskinesia –
Targeting Serotonin Receptors
Anders Björklund, MD, PhD
Professor, Department of Neurobiology
Wallenbery Neuroscience Center
Lund University
19

20. Development of a serotonin agonist as a treatment for dyskinesia
Therapeutic
Target Development Pre-Clinical Clinical Regulatory
Discovery Testing
Validation & Testing Approval
Optimization I II III
2005 Grant: Initial pre-clinical
testing
2008 Grant: Preclinical development
Available compound ID
2009 Grant: Clinical Trial funded
Industry partner - Psychogenics
20

21. Progress is being made in all areas of drug development
Therapeutic
Target Development Pre-Clinical Clinical Regulatory
Discovery Testing
Validation & Testing Approval
Optimization I II III
 MJFF has researched between 75-80% of targets being actively
investigated across the PD pipeline and has validated at least 6 novel
targets
 There are currently 139 drugs in the discovery phase for PD and 110 drugs
being tested in the clinic
 Growing interest with the pharmaceutical industry in PD drug development
21

22. Questions & Answers Session
 Anders Björklund, MD, PhD, Lund University
 Deborah W. Brooks, The Michael J. Fox Foundation
 John Dunlop, PhD, Pfizer, Inc., Neuroscience Research Unit
 Mark Frasier, PhD, The Michael J. Fox Foundation
 Irene Hegemen Richard, MD, University of Rochester
 Peter Reinhart, PhD, Proteostasis
 Todd Sherer, PhD, The Michael J. Fox Foundation
 Andrew Singleton, PhD, National Institute on Aging/NIH
22

23. Thank you for your participation!
For more information, please visit:
www.michaeljfox.org
Our 2011 Research Roundtable Series is generously
supported through an educational grant from Teva Neuroscience
23