Download Scientific Discoveries Allow Development of Targeted Therapeutics

Scientific Discoveries Allow
Development of Targeted Therapeutics
for Individuals with Autism Spectrum
Disorders
Randall L. Carpenter, M.D.
Co-Founder, President and CEO
August 9, 2012
Research Supported by:
NIMH, NICHD, NINDS
Best Pharmaceuticals for Children Act
FRAXA & Autism Speaks
Outline
• Our approach
• Challenges in translating scientific
discoveries into novel therapeutics
• Our case history
• Lessons learned
Vision and Strategic Focus
Translate Scientific Discoveries into Therapeutics that
Improve the Lives of Individuals with Autism
• Understand Causes of Autism
 Single gene disorders  pathogenesis  druggable targets
• Prioritize Disease-modifying Therapeutics
• Small, Smart POC Trials in Single Gene Disorders
• Bio-markers/signatures  Personalized Medicine
• Establish Broad Strategic Collaborations
Fragile X Syndrome
•
Most common known genetic
cause of autism and intellectual
disability
•
Results from mutation in a single
gene that prevents expression of
a single protein – FMRP
•
Function of FMRP conserved
from fly  fish  mouse
Seaside’s Approach to Translational Medicine in FXS
5
The Promise of Molecular Medicine
Human
with
Autism
Phase 2/3 Trials
(2012)
Novel
STX209
therapeutics
(2007)
Gene
discovery
Target ID and drug
development
Disease
models
Disease
pathophysiology
Basic neurobiology
6
STX209 Study in Individuals with ASD
• Study will complete this month, 150 subjects
–
–
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Double-blind, placebo-controlled, parallel group
12 weeks treatment duration
Age 5-21 years
Biomarker investigations
• Study results by end of year
7
Costs to Discover and Develop a New Drug
Basic
Research
209
107
$19mm, 5.5 years
$281mm
Traditional
Philanthropy
Government
& Universities
Pharma / Biotech
NIH
Financing Gap
Foundations
Venture Philanthropy
Angels
Venture
Capital
Private Equity
Public Markets
Paul SM, Nature Rev Drug Discov, 2010
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11
Phase 2/3 Clinical Trials Ongoing in FXS and Autism
Glutamate (and GABA) receptors at excitatory synapses
Presynaptic
axon terminal
Postsynaptic
dendritic spine
GABAB R
STX209
+
STX107
mGluR5
Pharmacologic Rescue with mGluR5 Inhibitors
• Efficacy in multiple animal models of fragile X
suggests evolutionary conservation
• As of April 1, 2012
- 40 distinct phenotypes
- 31 papers
13
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Fragile X
phenotype:
Corrected by
Corrected by
mGluR5 inhibition?
STX209?
Collaborator
Excess protein
synthesis


Peter Vanderklish
Scripps
Excess spine
density


Peter Kind
Edinburgh

Steve Warren
Emory

Richard Paylor
Baylor

Richard Paylor
Baylor
Excess AMPAR
turnover
Excess excitability
(AGS)
Excess marble
burying



15
15
Diverse genetic mutations converge on brain
signaling pathways that regulate synaptic function
Auerbach, Osterweil, Bear. Nature 2011
16
Mutations Causing Syndromic Autism Define an Axis
of Synaptic Pathophysiology
Auerbach, Osterweil, Bear. Nature 2011
17
Translational Medicine / Research
• Requires deep expertise and coordinated efforts in
multiple disciplines
– Large Pharma / Biotech
– Collaborations between Academics-IndustryNIH-Foundations-Venture Philanthropy
Seaside’s Collaborative Business Model
• Foundations – FRAXA, Autism Speaks/NAAR/CAN, NFXF
• Merck & Co, Inc. – Merck-Seaside mGluR5 NAM collaboration
• NIH UO1 Translational Research Cooperative Agreement
– NIMH, NICHD/BPCA, NINDS, FRAXA, Autism Speaks
• Baylor Medical Center – Richard Paylor, PhD
– Behavioral Research Collaboration (plus Autism Speaks and NIH)
• Vanderbilt University – P. Jeff Conn, PhD
– Vanderbilt Institute of Chemical Biology Program in Drug Discovery
• Academic Scientists and Clinicians
• Family Members and other Concerned Individuals
• F. Hoffman-La Roche Ltd – Roche-Seaside Alliance
Lessons Learned
• Fundraising is the biggest challenge
– We secured venture philanthropy seed funding
– Grant applications can augment funding
• Intellectual property is critical
– File patents for basic research discoveries
• use of Group I mGluR antagonists to treat disorders of
brain development (fragile X, autism)
– Our patents facilitated licensing mGluR5 antagonists from
Merck & Co Inc.
– GABA-B patents enable financing of STX209 development
• Collaborative business model is a necessity
Recommendations
• Focus on the ultimate goal - successful
development of novel therapeutics
–
–
–
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Resist incentives to over-value your contribution
Align shareholder interests
Share upside: 100% of nothing = nothing
Consider open-source initiatives
Translating breakthrough discoveries in
neurobiology into innovative drug treatments
that improve the lives of patients and families
with fragile X syndrome, autism and other
neurodevelopmental disorders