6th DRUG DISCOVERY FOR NEURODEGENERATION CONFERENCE:

An Intensive Course on Translating Research into Drugs

February 12-14, 2012 - New York City

Howard Fillit, MDExecutive Director, Alzheimer’s Drug Discovery Foundation

THANK YOU!

Funding for this conference was made possible in

part by

Cooperative Agreement U13AG031125-05 from

the

National Institute on Aging.

The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of

Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. 

Thank You!MEETING SPONSORS

  

  

BRONZE SPONSORS

SCIENTIFIC ADVISORY COMMITTEEKurt R. Brunden, PhD, University of Pennsylvania  

Neil S. Buckholtz, PhD, National Institute on Aging

Rebecca Farkas, PhD, National Institute of Neurological Disorders and Stroke

Howard Fillit, MD, Alzheimer’s Drug Discovery Foundation

Brian Fiske, PhD, Michael J. Fox Foundation for Parkinson’s Research  

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

Abram Goldfinger, MBA, New York University

Lorenzo Refolo, PhD, National Institute on Aging

Suzana Petanceska, PhD, National Institute on Aging

Diana Shineman, PhD, Alzheimer’s Drug Discovery Foundation

Edward G. Spack, PhD, Fast Forward, LLC

D. Martin Watterson, PhD, Northwestern University

SCIENTIFIC ADVISORY COMMITTEE

ADDF Staff

• Diana Shineman, PhD – Assistant Director, Scientific Affairs

• Rachel Lane, PhD – Scientific Program Manager

• Filomena Machleder – Assistant Director, Institutional Partnerships

• Natalie Romatz – Partnerships Assistant, Institutional Partnerships

• Niyati Thakker – Grants Assistant

• World Events Forum – Conference Secretariat

NOTES  

Please remember to complete and submit the meeting survey!

CME Certificates available at the Registration Desk

A webcast of the conference will be available soon on our website:

www.alzdiscovery.org

13th International Conference on Alzheimer’s Drug Discovery

 

 

September 10-11, 2012 • Jersey City, NJacross from NYC on the Hudson River

 

SAVE THE DATE!

Goals of the Meeting

• Knowledge:

– The principles and practice of drug discovery, with a focus on the unique aspects for neurodegenerative diseases

• Network:

– >190 attendees from 20 countries, ~40% from industry

– Exchange ideas, foster alliances, partnerships and collaborations

•WHO estimates neurodegenerative disorders will be the major unmet medical need of the 21st century, •surpassing cancer as the worlds’ second leading cause of death by the year 2040

Neurodegenerative Diseases Affect >22 Million Worldwide

Alzheimer’s disease; 5,000,000

Parkinson’s disease; 1,000,000

ALS; 30,000

Multiple sclerosis; 400,000 Huntington’s, 30,000

Some symptomatic agents, few disease modifying drugs

Developing a Drug is Risky, Takes 12-15 years and Costs Over $1.2B

1 FDAApproved

Drug

HUMAN STUDIES BIOLOGY

AND CHEMISTRY

ANIMALSTUDIES and

PHARMACOLOGY

InnovationProof

of MechanismSafety and

Proof of ConceptProof

of Efficacy

10,000 to>1 millionchemicals

Drug Discovery is a Vital Stage in Drug DevelopmentWhen Innovation is Created

Opportunity and Challenges for Success:A Perspective On The Origin of FDA Approved Drugs

From: T. Bartfai and GV Lees, Drug Discovery from Bedside to Wall Street, 2006;Le Couteur, et al 2011

Most are variants on formulation and delivery

Many anti-microbials

Less than 500 distinct chemical entities

Targeting ~266 human genome derived proteins

~50M compounds in Chem Abstracts;1040-10100 possible small molecules

20,000 human genes100,000 proteins

~10,000 approved drugs

Less than 50 unique chemical scaffolds

• Deposits of Misfolded Protein– Β-Amyloid, tau, α-synuclein, TDP-43, poly-Q aggregates

• Oxidative stress• Inflammation• Mitochondrial dysfunction• Synaptic and neuronal cell dysfunction• Vascular ischemia and damage• Other novel mechanisms (eg. epigenetics)

How a Biologist Thinks About Drug Discovery:Many Targets for Neurodegeneration?

• Target types– GPCR (small ligand)– Enzyme (small ligand)– Ion channel– Nuclear receptor– Protease– Enzyme (large ligand)– GPCR (large ligand)– Cytotoxic (other)– Protein kinase– Protein-protein

High

Success

Low

How a Chemist Thinks About Targets for Drug Discovery:Success Rates of Target Types

Why A Biological Network Approach to Drug Discovery is Needed: Signaling in the Synapse is Complex

How Were New Drugs Discovered? Phenotypic Screening Vs. Target-based

Screening

Swinney, et al, Nature Reviews Drug Discovery, July, 2011

Test for in vivo activity

Focused Medicinal Chemistry

Selection of leads

High throughput screen (500,000 cpds.)

Assay development

Screening approach

Inhibitor Development

Rational design approach

generation ofprotein

CrystalStructure

ComputerModel

MedicinalChemistry

PK

Specificity

Potency

Identification of hits

Case Studies: Routes to Drug Discovery

beta-secretase inhibitors gamma-secretase inhibitors

Improving Success Rates?Drug Discovery in Academia

• Drug discovery is the interface between basic research and clinical development

• Requires extensive resources and collaboration between teams of investigators

• Increasingly requires partnerships between pharma, biotechs, non-profits, and government, especially for neurodegenerative diseases

Drug Discovery and Development Requires Multidisciplinary Teams of Scientists

Clinical DevelopmentClinical Trialists

IND enabling studies: ADMET, formulation and scale-up chemistryPharamaceutical Scientists

In vivo Testing and Preclinical Proof of MechanismBiomarker Development

Animal Trialists

High Throughput Screening

Lead Identification and optimization

Structure Based Chemistry

Medicinal Chemistry, Pharmacology

Assay DevelopmentChemical Libraries

Computational Chemistry

Target identification Basic Neurobiology

The ADDF has granted over $55 million to >370 Alzheimer’s drug discovery programs in academic centers

and biotechnology companies in 20 countries 

ADDF funding has resulted in

>$2 billion in follow-on commitments,

and several novel drugs entering clinical trials

Feeding the Pipeline:The Alzheimer’s Drug Discovery

Foundation

www.AlzDiscovery.org

Drug Discovery: The “Valley of Death”? Or “Welcome to An Amazing Journey”!