Passion is our driver, strategy is our compass

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

2. Family Introductions

3. Proposed juvenile Batten treatment strategies Stem Cell Therapy Immuno-suppression 1 4 2 5 Gene Therapy TFEB Activation 3 6 Exon Skipping Other Small Molecule Initiatives

4. Stem Cell Therapies

5. Where do adult stems come from?

6. Approved for the treatment of Leukemia & Immune deficiencies

7. 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 disorders

8. 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

9. Gene Therapy CLN3

10. 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 underway • AAV9-hCLN3 gene therapy is licensed by Abeona Therapeutics • Abeona anticipates initiating a Phase I/II trial some time in 2017

11. Exon Skipping Drug “skips” over mistakes in the DNA Broken CLN3 Gene Child’s DNA Making a shorter but functional CLN3 gene Michelle Hastings, PhD | Rosalind Franklin University and Biogen Idec, MA

12. Immunosuppression Erika Augustine, MD, at the University of Rochester

13. TFEB Activation TFEB

14. Finding small molecules that activate TFEB

15. 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

16. 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 animals Dosing, Stability, Safety and Efficacy

17. Finding the right dose sideeffects adverse effect Peak level Onsetof effect Therapeuticwindow/Batten Disease Drug concentration desired response durationofeffect Sub-therapeutic Time

18. BBDF experimental planning 2016 Work packages 1 and 2 of EVT04117 Feb Mar April May CW 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 • PKs for WP1 • In vivo • Sample prep • Bioanalytic HH Evo16013 • PDs for WP2 • In vivo • MSD • Biochem assay • Western blot • Expro • Bioanalytic HH • In vivo • MSD • Biochemassay • Western blot • Expro • Bioanalytic HH Evo16012 Evo16021 Data reporting

19. 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

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