110/2/2009

Accelerated Research Collaboration

NASA Space Life Sciences

Innovation Lecture Series

July 9, 2009

Trailblazing for

Myelin Repair Treatments

10/2/2009 2

Agenda

1. Possible relevance to NASA

2. The status quo in medical research – a broken system

3. MRF’s solution - the evolving ARCTM model

4. Summary

5. Q&A

10/2/2009 3

Possible Relevance to NASA Space Life Sciences

Begin with the end in mind

Ignorance can be beneficial

Science can be accelerated

Innovation can be managed

Creativity can be enhanced

Add value to all participants

Never ending flexibility and problem solving

Convince and cajole not command and control

10/2/2009 4

MS and Myelin

Multiple Sclerosis

• Damage in CNS

• Typical impacts

• Increasing incidence

• Complex disease

• No exact animal model

• Auto immune disease?

• Why 70% women?

Myelin

• “Insulation” on axons

• Key to MS, depression and many other diseases

10/2/2009 5

Why is the MRF Necessary?

The problem• In 2001 the potential for myelin repair was underappreciated.

• The system is broken.

The vision• An entirely new approach to greatly accelerate getting treatments to

patients.

The goal• Develop and demonstrate a new model to accelerate new treatments

for ALL diseases.

• License the first myelin repair target to biopharma within five years.

10/2/2009 6

Traditional Model for Medical Research - Past

10/2/2009 7

Traditional Model for Medical Research

Past Present

10/2/2009 8

Pharmaceutical R&D output flat despite increasing

spend...

1. IMDs (Incrementally Modified Drugs) are new derivatives, formulations and combinations2. NME (New Molecular Entities) include both chemical and biological therapeutic agents, excludes contrast agents and diagnosticsSource: FDA, PhRMA 2005 Yearbook

…but NME approvals relatively flat

0

70

140

’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ’02 ’03 ’04 ’05

No. of approvals

NMEs

INDs

R&D spending has grown steadily…

0

15

30

45

’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ’02 ’03 ’04 ’05

($B)

CAGR

11.3%

CAGR

10.5%

Domestic R&D

R&D abroad

10/2/2009 9

100 Labs

Worldwide

Biogen/

IDEC

Barres

Lab

Popko

LabS. Miller

Lab

R.Miller

LabBasic

Research

Target

Discovery

Drug

Discovery

Target

Validation

Myelin Repair Research Landscape - 2002

10/2/2009 10

There are many steps required to get a new

therapeutic to patients

10/2/2009 11

10/2/2009 12

Myelin Repair Discovery Biology

Six Areas of Research

1. Understanding how oligodendrocytes

are normally generated from neural

stem cells and how MS perturbs this

process

2. Understanding the underlying

mechanism of myelination and how

it is perturbed in MS

3. Understanding how nodes of Ranvier

and paranodes are normally formed

and how they are perturbed in MS

4. Understanding the immune response

in MS and how inflammation affects

myelin repair

5. Understanding how the Blood Brain

Barrier is affected in MS and its role

in the disease

6. Development of better animal

models for study of MS and

remyelination.

10/2/2009 13

Major Milestones Achieved since 2004

~ 19 new targets/pathways identified

> 24 new research tools, assays and models developed

9 patent applications filed and 8 in prep (first patent awarded 2008)

> 75 publications in peer-reviewed journals

Recognized by the media, academics and non-profits for developing a breakthrough model for medical research

Biopharma now views myelin repair as a viable therapeutic area

10/2/2009 14

Basic

Research

Target

Discovery

Target

Validation

Repair

Blood

Brain

Barrier

Repair by

Stem

Cells

Protection

from

Inflammation

Stimulating

Repair

in Lesions

Immune

Regulation

+ Myelin

Promotion

Biomarker

Discovery

Partners

Biomarkers

Molecular

Biomarkers

MRF Tool Box

Barres

Lab

Popko

Lab

S. Miller

Lab

R.Miller

Lab

Human

Neural

Assay

Center

MRF Research Plan

Protocol

Development

MRF Research Landscape - 2009

Industry

Partner(s)?

Industry

Partner?Drug

Discovery

10/2/2009 15

Crossing the Valley of Death –Accelerating the transition from promising targets to clinical candidates

0

200

400

600

800

1,000

Target ID Validation Screening Lead opt Pre-clin Phase I Phase II Phase III NDA Total

Percentage of total cost of success

$880M

19%

23%

5%

10%

7%

10%

11% 1%

Source: BCG economic model study in Biomedical Industry Advisory Group, 2005; BCG clinical development model, 2007

Target

Validati

on

Screen-

ing

Target

ID

Optimi-

zation

Pre-

clinical

Phase

I

Phase

II

Phase

III

Filing

NDA

14%

71% of industry costs

1.0 0.4 2.7 1.5 1.5 2.5 1.5 14.72.0 1.6Avg.

time (yr)

ARC Expansion

15 - 30

Cost

($M)

Basic

Research

MRF’s ARC Model Proposed ARC Expansion

10/2/2009 16

The Drug Discovery process is essential for

• The continued success of the MRF

• The development of a therapeutic

MRF’s research model has efficiently produced many novel myelin repair targets

The drug discovery process operates on a different set of requirements, skill sets, experience and scientific criteria than academic target identification.

Because of the significant cost to develop a therapeutic, industry requires a very compelling and comprehensive data package prior to the investment of resources on a drug target.

Extending the MRF’s Research Model into Drug Discovery

10/2/2009 17

Progress Toward Developing Myelin Repair Treatments

Internal drug discovery team

Drug Discovery Advisory Group (DDAG)

Partnering/Licensing Strategy

10/2/2009 18

Therapeutic Approach Target/Pathway Target Discovery Drug Discovery Preclinical Phase 0/I Phase IIa

Immunomodulation Induced Cell Tolerance

Immunomodulation MSC

Immunomodulation Costimulatory Blockade

Immunomodulation MDC blockade

Immunomodulation Costimulatory Blockade

Protect Myelinating OPCs ISR Antagnoist

Protect Myelinating OPCs ISR gene

Enhance OPC Migration and Lesion Penetration Cytokine Receptor Antagonist

Enhance OPC Migration and Lesion Penetration Migration & Expansion Enhancer

Enhance OPC Migration and Lesion Penetration Migration Promoter

Enhance OPC Migration and Lesion Penetration Migration Enhancer

OPC Differentiation/Enhance Remyelination Differentiation Promoter

OPC Differentiation/Enhance Remyelination Differentiation Controller

OPC Differentiation/Enhance Remyelination Differentiation Controller

OPC Differentiation/Enhance Remyelination Differentiation Controller

OPC Differentiation/Enhance Remyelination Myelination Controlle r

Repair Blood Brain Barrie r Tight Junction Formation

Repair Blood Brain Barrie r Tight Junction Formation

Myelin Repair Foundation Pipeline 2009

10/2/2009 19

Strategies for Translating MRF Discoveries

Support existing pharma company pipelines• Offer access to MRF Target Validation toolkit

• Provide data for “repurposing” existing clinical candidates

Contracting• Promote research collaborations with corporate entities

• Fund Target Validation/Drug Discovery studies at CROs

Partnering• Offer exclusive licensing options to MRF targets/tools

• Create Joint IP with biotech/pharma partners

Spinoffs• Create new corporate entities to develop innovative MRF programs

10/2/2009 20

Relevance to NASA Space Life Sciences

Collaboration is intellectually stimulating and very productive

Many teams vs. single large team

Creative problem solving

The ARC model could be a starting point

Encourage risk taking and entrepreneurism

Set audacious goals

Keep it fun

10/2/2009 21

The only non-profit medical research

foundation that participates in the entire

continuum of drug discovery

10/2/2009 22

Summary

MRF began with a specific, narrow, measurable audacious goal

MRF set out to accelerate all elements in the value chain

MRF convenes experts to help solve problems as they become evident

MRF uses its non-profit status to the fullest advantage

MRF has made remarkable progress

The second five years will require $100M

Networking is critical to achieving our goals

www.myelinrepair.org