May 6 2016 Family Introductions Proposed juvenile Batten treatment strategies Immunosuppression Stem Cell Therapy Gene Therapy Exon Skipping TFEB Activation Other Small Molecule Initiatives ID: 527648
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Slide1
Passion is our driver, strategy is our compass
May 6, 2016Slide2
Family IntroductionsSlide3
Proposed juvenile Batten treatment strategies
Immuno-suppression
Stem Cell Therapy
Gene Therapy
Exon Skipping
TFEB
Activation
Other
Small Molecule
Initiatives
6
2
1
5
4
3Slide4
Stem Cell Therapies Slide5
Where do adult stems come from? Slide6
Approved for the treatment of Leukemia & Immune deficienciesSlide7
Stem Cell Therapy and Batten Disease
BBDF and the New York Stem Cell Foundation
Sanford
Children’s Health Research Center
Duke University Clinical Trial in Lysosomal Storage Diseases and inherited metabolic disordersSlide8
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 CLN3Slide9
Gene Therapy
CLN3Slide10
Recent progress in CLN3 Gene Therapy
October 2014: Very first demonstration that a gene like CLN3 could be used in gene therapy
April 2016: BBDF supports Dr
. Tammy
Kielian’s safety
and efficacy data
describing
an intravenous gene therapy approach for juvenile Batten disease.
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
Additional preclinical studies are underwayAAV9-hCLN3 gene therapy is licensed by Abeona Therapeutics Abeona
anticipates initiating a Phase I/II trial some time in 2017Slide11
Exon Skipping
Drug “skips” over mistakes in the DNA
Broken
CLN3
Gene
Child’s DNA
Michelle Hastings, PhD | Rosalind Franklin University
and Biogen Idec, MA
Making a shorter but functional CLN3 geneSlide12
Immunosuppression
Erika Augustine, MD, at the University of RochesterSlide13
TFEB Activation
TFEBSlide14
Finding small molecules that activate TFEBSlide15
Sardiello results with TFEB activating compound:
Inhibits the onset and lessens the severity of motor and cognitive symptoms
Induces clearance of cellular waste
Increases the life
span of
Batten mice
Activates TFEB
Prevents loss of brain mass over timeSlide16
Preparing for the FDA
Pharmacokinetics
(PK)
(What the body does to the drug
)
Information on the absorption, distribution, metabolism, and excretions of a
drug
Pharmacodynamics (PD)
(What the drug does to the body) Description of the pharmacologic effects and mechanism(s
) of actions of a drug in animalsDosing, Stability, Safety and EfficacySlide17
Finding the right dose
a
dverse
effect
d
esired
response
Sub-
therapeutic
s
ide
effects
Drug concentration
Time
Onset
of
effect
Therapeutic
window
/Batten
Disease
duration
of
effect
Peak
levelSlide18
09
BBDF experimental planning 2016
18
Work packages 1 and 2 of EVT04117
PKs for WP1
In vivo
Sample prep
Bioanalytic HH
PDs for WP2
In vivo
MSD
Biochem assay
Western blot
Expro
Bioanalytic
HH
In vivo
MSD
Biochem
assay
Western
blot
Expro
Bioanalytic
HH
CW
May
Feb
17
18
19
20
05
06
07
08
Mar
10
11
12
13
16
April
14
15
Data reporting
Evo16012
Evo16013
Evo16021Slide19
Other Small Molecule Therapy Programs
Tammy Kielian, PhD at the University of Nebraska and PfizerINI-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
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 EvotecScreening of over 430,000 compounds
National Center for Advancing Translational Sciences (NCATS) Over 400,000 FDA-approved compounds Slide20
Passion is our driver, strategy is our compass
Thank you!