Passion is our driver, strategy is our compass May 6, 2016

Family Introductions

Proposed juvenile Batten treatment strategies Immuno- suppression Stem Cell Therapy Gene Therapy Exon Skipping 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 Broken CLN3 Gene Child’s DNA Michelle Hastings, PhD | Rosalind Franklin University and Biogen Idec, MA Making a shorter but functional CLN3 gene

Immunosuppression Erika Augustine, MD, at the University of Rochester

TFEB Activation TFEB

Finding small molecules that activate TFEB

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 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

Finding the right dose adverse effect desired response Sub-therapeutic side effects Drug concentration Time Onset of effect Therapeutic window/Batten Disease duration of effect Peak level

PAGE 09 BBDF experimental planning 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 Mar April 1415 Data reporting Evo16012 Evo16013 Evo16021

Other Small Molecule Therapy Programs  Tammy Kielian, PhD at the University of Nebraska and Pfizer » 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 » 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

Passion is our driver, strategy is our compass Thank you!