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”!