MJFF Strategy forAccelerating Developmentof Parkinson’s Therapies

Research RoundtableChicago, IllinoisJune 27, 2011

Today’s Agenda

MJFF OverviewDeborah W. Brooks The Michael J. Fox Foundation for Parkinson’s Research

MJFF Program HighlightsSonal S. Das, PhD The Michael J. Fox Foundation for Parkinson’s Research

PanelistsChristopher G. Goetz, MD

Rush University Medical Center

Jeffrey H. Kordower, PhDRush University Medical Center

Tanya Simuni, MD Northwestern University

Glenn T. Stebbins, PhDRush University Medical Center

Questions & Answers Session

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MJFF Overview

Deborah W. BrooksCo-Founder/Executive Vice Chairman

The Michael J. Fox Foundation for Parkinson’s Research

Parkinson’s disease: Defining the need

Parkinson’s disease (PD) is a progressive neurodegenerative disease that affects nearly one million Americans; related Parkinsonisms affect an additional half million Americans.

PD prevalence is expected to grow sizably over the next 25 years as the proportion of older Americans continues to increase.

Significant therapeutic needs exist:

– Current therapies to treat motor and non-motor symptoms are inadequate leaving substantial unmet needs for those living with PD.

– There is currently no therapy proven to modify the progression of the disease.

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MJFF was founded with clear objectives

Drive the Best Parkinson’s Research

Deliver Improved Therapies and a Cure

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In 2010, we received nearly 65,000 contributions and raised $57M.

Core values are efficiency and accountability: nearly 90 cents of every $1 spent goes straight to research program efforts. We work to redeploy all donations quickly. We have no endowment or excess reserves.

Since founded in 2000, MJFF has funded more than $240M in research

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Our in-house staff of 7 PhDs and 6 business strategists serve as portfolio managers, incorporating the advice and input of experts from academia and industry into their decision-making.

In 2010, we reviewed over 800 PD-specific grants and currently have roughly 250 active grants in our portfolio.

(est.)

Discovery Target Validation

Therapeutic Development

& Optimization

Pre-Clinical Testing

Clinical Testing

I II III

Regulatory Approval

Progress requires translation of discoveries through the pipeline

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PreclinicalConvert biology into therapies Partly done in academic and

biotech laboratories

ClinicalDetermine safety and efficacy

in patientsMostly done by large pharma

$680 million/year

Basic DiscoveryUnderstanding disease

mechanismsMostly done by academics

$156 million/year

Unique opportunity for MJFF’s strategic funding/leadership to bridge the gap

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Our approach has evolved as we’ve grown and learned

2000-05

2005-11

Focus on research is required to move the needle

The science is ahead of the money

We are not a bank, assets must be deployed quickly to the best science

Our goal is to go out of business 10-year horizon ________________________________________________________________________________________________________________________

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MJFF grant-making cannot be done in a vacuum – a comprehensive view of the landscape is key

Strategy must focus on tackling roadblocks to progress in a systemic fashion, i.e. target validation, research tools, clinical trial design, recruitment

More proactive outreach and engagement with industry partners is required

Turning our knowledge out can ensure others benefit from the field knowledge we are developing

MJFF is in a unique position to bring all constituents together in the name of faster progress

Problem-solve: lead and innovate

Prioritize critical research

Facilitate handoffs and orchestrate connections Showcase top ideas to industry Tirelessly pursue smart, creative solutions to

challenges

Craft aninformed agenda

Understand needs of patients

View global field and identify most promising targets

Convene experts in non-competitive environment

Infuse capital at underfunded, high-risk stages Develop and share essential tools Pragmatically push research in a goal-directed,

milestone-driven fashion

DE-RISK PD 9

How does MJFF work to accelerate progress today?

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2011 MJFF Program HighlightsNeed for Disease-Modifying Therapies

Biomarkers and The Parkinson’s Progression Markers Initiative

Improving Symptomatic Treatments

Sonal S. Das, PhDAssociate Director, Research Programs

The Michael J. Fox Foundation for Parkinson’s Research

MJFF priority area efforts drive progress in key research topics

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Alter Disease

Validate Genetic Targets

Develop Trophic Factors

Define PD/PD Progression

Develop Biomarkers of PD Progression

Improve PD Clinical/Pathological

Understanding

Treat Symptoms & Side Effects

Dyskinesias

Non-Motor Symptoms

(Cognitive/Mood, Posture/Gait)

Altering the course of PD: Need for Disease-Modifying Therapies

Current Targets Rationale – Why prioritize?

Trophic Factors

Hypothesis for use of trophic factors to treat PD remains viable and exciting Pre-clinical and early phase clinical results continue to show promise

LRRK2

Mutations in LRRK2 may be most common genetic cause of PD Protein kinase function makes LRRK2 a highly druggable target

Alpha-Synuclein Pathological presence in Lewy bodies of familial and sporadic PD Genetic association in familial cases of PD

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MJFF has committed over $100M to advance disease modifying therapies and seeks a path forward to patients.

Expert Insight, Jeffrey H. Kordower, PhD

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Disease-Modifying Therapies

Jeffrey H. Kordower, PhDDirector, Research Center for Brain Repair

The Jean-Schweppe Armour Professor of Neurological SciencesRush University Medical Center

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Obstacles include:

• Current trial paradigm requires large number of subjects

• Efficacy testing is a long process, diminishing patent value

• Reliance on clinical measures alone confound trial interpretation

• There are no biological indications of underlying disease that complement clinical changes

Markers of progression are essential to achieve near-term hopes for needed therapies

Challenges remain in testing disease-modifying therapies

Biomarkers

Therapeutic MarkersProgression MarkersDiagnostic Markers

Identify PD patients and, perhaps, even determine who is at risk for developing PD

Assist with patient selection for clinical studies…Are we studying the right population of people?

Facilitate measurement of modifications in the disease - could provide valid clinical trial endpoints

Help guide clinical trial design parameters like patient numbers, stratification, duration of treatment

Is the therapeutic reaching its target?

Is the therapeutic having its desired effect?

Without markers of progression, clinical trials to test new therapies in patients are at risk of yielding

inconclusive results

MJFF has supported almost $31M in biomarker discovery

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The Parkinson’s Progression Markers Initiative (PPMI)

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PPMI

Dataset/ sample

collection

Standardized protocols

Biomarker verification

studies

Identify progression

markers

PPMI is a ground-breaking clinical study that aims to dramatically accelerate PD drug development by identifying biomarkers of the disease. PPMI aims to recruit 400 newly diagnosed people with Parkinson’s and 200 control participants.

A pre-competitive collaboration between government and industry.

A study of this size – $45M over a 5 year period – requires large scale funding: Abbott, Biogen Idec, Covance, GE Healthcare, Genentech, Merck, Pfizer and Roche are lead industry supporters.

As of Wednesday, June 22nd, 2011, 19 out of 21 PPMI sites in the US and Europe are currently recruiting volunteers. At these sites, 140 participants have been recruited (82 PD, 58 control) with an additional 43 consents.

Expert Insight, Tanya Simuni, MD

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Insights Into PPMI and What We Hope to Learn

Tanya Simuni, MDA.C. Nielsen Research Professor of Parkinson's disease

Associate Professor of NeurologyDirector, Parkinson’s Disease and Movement Disorders Center

Northwestern University

Clear need for developing treatments for motor & non-motor symptoms

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Dyskinesia

Non-Motor Symptoms

MJFF has funded nearly $17M in dyskinesia research and $18.5M in research towards improving treatments for 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 leads to a better quality of life for those living with PD

MJFF is funding two parallel tracks in dyskinesia research:

1. Developing new therapies 2. Determining how to best assess these therapies in the

clinic (Dyskinesia Rating Scale Study)

Expert Insight: Christopher G. Goetz, MD

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Advancing Treatments for Dyskinesia

Christopher G. Goetz, MDProfessor of Neurological Sciences

Professor of PharmacologyRush University Medical Center

Co-Principal Investigator, Dyskinesia Rating Scale

Glenn T. Stebbins, PhDProfessor of Neurological Sciences

Rush University Medical CenterCo-Principal Investigator, Dyskinesia Rating Scale

Empowered coordinators

Smart matches

Active alert system

Robust content

Connecting willing volunteers with clinical trials in their area

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50% of clinical trial sites that enroll 1 or 0 subjects in their studies 85% of clinical trials finish late due to recruitment troubles Estimates hold that fewer than 1 in 10 people with Parkinson’s

participate in clinical trials

Questions & Answers Session

Deborah W. Brooks, The Michael J. Fox Foundation for Parkinson’s Research

Sonal S. Das, PhD The Michael J. Fox Foundation for Parkinson’s Research

Christopher G. Goetz, MD Rush University Medical Center

Jeffrey H. Kordower, PhD Rush University Medical Center

Tanya Simuni, MD, Northwestern University

Glenn T. Stebbins, PhD, Rush University Medical Center

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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!