Transcript Passion is our driver, strategy is our compass

May 6, 2016
Passion is our driver, strategy is our compass
Family Introductions
Proposed juvenile Batten treatment strategies
Stem Cell Therapy
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Gene Therapy
Exon Skipping
Immunosuppression
TFEB
Activation
Other
Small Molecule
Initiatives
Stem Cell Therapies
Where do adult stems come from?
Approved for the treatment of Leukemia & Immune deficiencies
Stem Cell Therapy and Batten Disease
1. BBDF and the New York Stem Cell Foundation
2. Sanford Children’s Health Research Center
3. Duke University Clinical Trial in Lysosomal Storage Diseases
and inherited metabolic disorders
What is Gene Therapy?
 Gene therapy involves inserting corrective
genes (DNA) designed in the laboratory, into
the genetic material of a patient's cells to
treat his genetic disease
 Give children with broken CLN3 genes a
synthetic copy of CLN3
Gene Therapy
CLN3
Recent progress in CLN3 Gene Therapy
1. October 2014: Very first demonstration that a gene like CLN3 could be used in
gene therapy
2. April 2016: BBDF supports Dr. Tammy Kielian’s safety and efficacy data
describing an intravenous gene therapy approach for juvenile Batten disease.
3. Adeno-associated virus 9 (AAV9) vector carrying a synthetic CLN3 gene is able
to improve motor and cognitive deficits, as well as lessen inflammation in a
CLN3 mouse model
4. Additional preclinical studies are underway
5. AAV9-hCLN3 gene therapy is licensed by Abeona Therapeutics
6. Abeona anticipates initiating a Phase I/II trial some time in 2017
Exon Skipping
Drug “skips” over mistakes in the DNA
Child’s DNA
Broken
CLN3
Gene
Making a shorter but functional CLN3 gene
Michelle Hastings, PhD | Rosalind Franklin University
and Biogen Idec, MA
Immunosuppression
Erika Augustine, MD, at the University of Rochester
TFEB Activation
Finding small molecules that activate TFEB
Sardiello results with TFEB activating compound:
Activates TFEB
Induces clearance of cellular waste
Inhibits the onset and lessens the severity of motor and cognitive symptoms
Increases the life span of Batten mice
Prevents loss of brain mass over time
Preparing for the FDA
1) Pharmacokinetics (PK) (What the body does to the drug) Information on the absorption,
distribution, metabolism, and excretions of a drug
2) Pharmacodynamics (PD) (What the drug does to the body) Description of the pharmacologic
effects and mechanism(s) of actions of a drug in animals
3) Dosing, Stability, Safety and Efficacy
Drug concentration
Finding the right dose
side effects
adverse effect
Onset of
effect
Peak level
Therapeutic window/Batten Disease
duration of effect
desired response
Sub-therapeutic
Time
BBDF experimental planning 2016
Work packages 1 and 2 of EVT04117
Feb
CW
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April
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PKs for WP1
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In vivo
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Sample prep
Evo16013
 Bioanalytic HH
PDs for WP2
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In vivo
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MSD
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Biochem assay
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Western blot
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Expro
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Bioanalytic HH
Evo16012
Evo16021
PAGE
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In vivo
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MSD
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Biochem assay
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Western blot
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Expro
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Bioanalytic HH
Data reporting
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Other Small Molecule Therapy Programs
 Tammy Kielian, PhD at the University of Nebraska and Pfizer
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INI-0602, is a novel hemichannel inhibitor that reduces glutamate accumulation +/Roflumilast, shown to reduce inflammation and preserve brain function in mouse
models of Alzheimer’s and Huntington’s disease
 Kenneth Hensley, PhD at the University of Toledo and Xonovo
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XN-001 has been shown to stimulate cellular clearance in animal models of
Alzheimer’s disease, Muscular Dystrophy, and juvenile Batten disease
 Andrea Ballabio, MD at Texas Children’s and TIGEM
» Screening of 1200 FDA-approved compounds small enough to enter the brain
 Rainer Kuhn, PhD at Evotec
» Screening of over 430,000 compounds
 National Center for Advancing Translational Sciences (NCATS)
» Over 400,000 FDA-approved compounds
Thank you!
Passion is our driver, strategy is our compass