MJFF’s Purpose, Promise and Plan forSpeeding New Parkinson’s

Treatments to PatientsResearch RoundtableNew York, New YorkNovember 12, 2011

Today’s Agenda

MJFF OverviewDeborah W. Brooks

The Michael J. Fox Foundation for Parkinson’s Research

MJFF Research Progress & Remaining ChallengesTodd Sherer, PhD

The Michael J. Fox Foundation for Parkinson’s Research

PanelistsAnders Björklund, MD, PhD

Lund University

John Dunlop, PhDPfizer, Inc., Neuroscience Research Unit

Mark Frasier, PhDThe Michael J. Fox Foundation for Parkinson’s Research

Questions & Answers Session

2

3

MJFF Overview

Deborah W. BrooksCo-Founder & Executive Vice Chairman

The Michael J. Fox Foundation for Parkinson’s Research

Why we exist…

Drive the Best Parkinson’s Research

Deliver Improved Therapies and a Cure

4

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.

0102030405060

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

new

co

mm

itm

en

tsin

millio

ns

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.

With over $270M funded since 2000, we are on a mission to speed a cure

5

(est.)

Discovery Target Validation

Therapeutic Development

& Optimization

Pre-Clinical Testing

Clinical Testing

I II III

Regulatory Approval

Drug development is long, costly and risky…but can be smarter

6

MJFF steps in to drive translation and assure that promising therapies get

closer to patients

ClinicalDetermine safety and efficacy

in patientsMostly done by large pharma

$680 million/year

Basic DiscoveryUnderstanding disease

mechanismsMostly done by academics

$156 million/year

PreclinicalConvert biology into therapies Partly done in academic and

biotech laboratories

7

2011 MJFF Research Progress and

Remaining Challenges Altering Disease: Disease Modifying Therapies

LRRK2: A Collaborative ExampleRepositioning Drugs

Improving Symptomatic TreatmentsTargeting Serotonin Receptors

Todd Sherer, PhDChief Executive Officer

The Michael J. Fox Foundation for Parkinson’s Research

There are numerous therapeutic needs for PD patients

8

Alter Disease

Validate Genetic Targets

Develop TrophicFactors

Treat Symptoms & Side Effects

Dyskinesias

Non-Motor Symptoms

Biological PathwaysRestoration of Dopamine Cause of PD

Alpha-Synuclein: Genetic association in familial cases of PD; pathology evidence

LRRK2: Protein kinasefunction makes LRRK2 a highly druggable target

Trophic Factors: Data continues to show promise that increasing the levels of trophic factors can protect brain cells in PD

Inflammation: Inhibiting inflammation could slow the progression of PD

Oxidative Stress:Decreasing oxidative stress can protect dopamine neurons

Multiple approaches to altering the course of PD

9

MJFF has committed nearly $115M to advance disease modifying therapies

MJFF LRRK2 efforts are driving research towards the clinic

10

MJFF focuses on four key areas within LRRK2 research, reducing research redundancies and facilitating collaborations among investigators

– over $38M spent on LRRK to date

Develop LRRK2

research tools

Supports LRRK2

therapeutic development

Study LRRK2 impact

clinically

Improve understanding

of LRRK 2 biology

LRRK2 Biology Consortium – A Collaborative Example

11

• Agree to share data and tools

• Overlapping approaches

Over 20 sites worldwide

• Website –protocols and data

• Monthly calls and annual summit meeting

Mechanisms for sharing • Prototype

compound shared with 18 teams

• Novel collaborative projects developed between teams

Tangible interactions

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.

Expert Insight: John Dunlop, PhD

12

LRRK2 Consortium: How collaborative science is accelerating drug development

John Dunlop, PhDChief Operating Officer

Neuroscience Research UnitPfizer

13

Preclinical Studies

Phase I safety in controls

Phase I safety in

PD patientsPhase II/III

efficacyRegulatory Approval

Repositioning compounds may lead to disease altering therapies

Traditional drug development pipeline

Acceleration by repositioning drugs that are deemed “safe” 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

Preclinical Studies

Phase I safety in controls

Phase I safety in

PD patientsPhase II/III

efficacyRegulatory Approval

Expert Insight, Mark Frasier, PhD

14

Repositioning Pioglitazone: From Diabetes to PD

Mark Frasier, PhDDirector, Research Programs

The Michael J. Fox Foundation for Parkinson’s Research

1515

Repurposed drug made ready for significant NIH support

Discovery Target Validation

Therapeutic Development

& Optimization

Pre-Clinical Testing

Clinical Testing

I II III

Regulatory Approval

Pioglitazone as a disease-modifying therapy

2004 Grant: Pre-clinical testing

2007 Grant: Dosing and BioavailabilityAvailable compound ID

2010: NIH funded clinical trial

MJFF brokers introduction to clinicians

2010: MJFF supports biomarker add on

Multiple promising trials and approaches are taking place

16

Novel Drug Targets

Trophic Factors/Ceregene Hypothesis for use of trophic factors to treat PD

remains viable and exciting Pre-clinical and early phase clinical results

continue to show promise

AFFITOPE PD01 Attempts to remove alpha-synuclein protein

aggregates First time a vaccine approach has been tested

in the clinic for PD

Repositioned Compounds

Isradipine Calcium channel blocker for hypertension Found to be neuroprotective in pre-clinical

models of PD

Inosine Increasing urate levels could both lower the risk

of getting PD and slow the progression of the disease

Nicotine Smoking linked to decreased risk of PD First test as a disease-modifying therapy in PD

Clear need to develop treatments for motor & non-motor symptoms

17

Dyskinesia

Non-Motor Symptoms

MJFF has funded over $40M in research towards developing treatments for both treating dyskinesia and non-motor symptoms.

Uncontrolled body movements that result from dopamine-replacement therapy

Breakthroughs in treating dyskinesia would expand options for treating PD

Includes cognitive dysfunction, anxiety, memory loss and mood disorders

Relieving these symptoms would lead to a better quality of life for those living with PD

Funding two parallel tracks for improving symptomatic treatments

18

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?

mGluR5

Shown to reduce levodopa induced dyskinesiain pre-clinical studies

Addex Pharmaceuticals and Novartis are conducting trials to test mGluR5 antagonists in PD patients

L-Dopa Delivery New methods of delivering levodopa that will

result in constant blood levels compared to “peaks and valleys” currently experienced

Neurologix Non-dopamine gene therapy strategy in

development Designed to normalize brain physiology and

reduce the symptoms of PD

Droxidopa Repurposing droxidopa (orthostatic

hypotension) in an effort to see if it can abate gait, sleep and cognitive disorders in PD

Serotonin Receptors Targeting serotonin receptors could be key in reducing dyskinesia

Expert Insight: Anders Björklund, MD, PhD

19

Advancing Treatments for Dyskinesia –Targeting Serotonin Receptors

Anders Björklund, MD, PhDProfessor, Department of Neurobiology

Wallenbery Neuroscience CenterLund University

2020

Discovery Target Validation

Therapeutic Development

& Optimization

Pre-Clinical Testing

Clinical Testing

I II III

Regulatory Approval

2005 Grant: Initial pre-clinical testing

2008 Grant: Preclinical development

Available compound ID

2009 Grant: Clinical Trial fundedIndustry partner - Psychogenics

Development of a serotonin agonist as a treatment for dyskinesia

21

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

Discovery Target Validation

Therapeutic Development

& Optimization

Pre-Clinical Testing

Clinical Testing

I II III

Regulatory Approval

Progress is being made in all areas of drug development

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

For more information, please visit:

www.michaeljfox.org

Our 2011 Research Roundtable Series is generously supported through an educational grant from Teva Neuroscience

Thank you for your participation!