Prothelia

1. Prothelia Therapeutics for the Muscular Dystrophies

2. Prothelia • Mission • Increase the longevity and quality of life of patients with muscular dystrophy • Lead Drug Candidate – LAM-111 • Delivered systemically to MDC1A and DMD mouse models • Excellent efficacy with no toxicity • Human LAM-111 in human MDC1A and DMD cells • Human LAM-111 in mouse MDC1A and DMD muscle cells • Stable and scalable human LAM-111 manufacturing process • Under evaluation for treatment of dystroglycanopathy and dysferlinopathy Ashley

3. A picture is worth…. SAM No LAM-111 Human LAM-111

4. Happy Birthday…. Adelina Merosin Deficient (MDC1A) mice have a reduced lifespan and normally live between 6-15 weeks of age, so 1 year is a very significant milestone Picture provided by Prothelia collaborator Dr. Dean Burkin, University of Nevada, Reno Merosin Deficient (MDC1A) mouse treated with laminin-111 (10mg LAM-111/kg/week starting at 10 days of age) What does it take to bring LAM-111 to clinical trials?

5. Successful Drug Development Requires a collaborative Effort Preclinical models Natural history Patient identification and accrual Investment Drug manufacture Animal testing Clinical testing Project coordination Investment Industry Science Drug Development Program Maia Development incentives Funding support Regulatory guidance Rare Disease Program (HTS etc) Government Advocacy Patient referral Trial promotion Investment

6. Drug Development Aubrey

7. Bottlenecks in Drug Development Philip

8. Cost of Developing a New Drug*(“New Chemical Entity”) * Data from Pharma drugs developed entirely in-house Pierce Only 1 in 13 Candidates Succeed 3 in 5 Phase III Trials Succeed Adams CP, Brantner VV (2010) “Spending on New Drug Development” Health Econ. 19: 130–141 (2010)

9. Clinical Trial Costs* Jake Phase I: About $15K/person Phase II: About $19K/person Phase III: About $26K/person *LifeSciences World 10/13/2006 • What the non-profit and government communities have done (funded): • Funding the “Valley of Death” • Developing International Patient Registries • Developing Clinical Research Networks • Developing and Validating Clinical Endpoints • Developing Natural History to accurately power studies • Standards of Care • Areas of improvement: • We need biomarkers to decrease testing time • We need novel trial designs to reduce costs and time • We need centralized IRBs • We need electronic medical records • We need clinical data standards • We need harmonization between the FDA and EMEA

10. Prothelia’s Scientific and Medical Advisory Board (SMAB) • Brad Hodges, PhD Chairman, SMAB; CSO, Prothelia, Inc. • Dean Burkin, PhD Lead Investigator; Director, Nevada Transgenic Center for Biomedical Research Excellence, Associate Professor, University of Nevada School of Medicine • Ed Connor, MD Director, Office of Investigational Therapeutics at Children's National Medical Center and Professor of Pediatrics at George Washington University School of Medicine and Health Sciences • Eric Hoffman, PhD Chairman, Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences and Director, Research Center for Genetic Medicine at Children's National Medical Center • George Vella, PhD Director of Research and Strategic Planning, Charley’s Fund • John M McCall, PhD President, PharMac LLC • Markus A Ruegg, PhD Professor of Neurobiology, Biozentrum University of Basel • Steve D Hauschka, PhD Professor of Biochemistry, University of Washington Kyra

11. Support • Scientists/Clinicians • Jim Collins, MD, PhD Assistant Professor of Pediatric Neurology, University of Cincinnati College of Medicine, Pediatric Neurologist, Cincinnati Children’s Hospital Medical Center • Jim Dowling, MD, PhD Assistant Professor, Division of Pediatric Neurology, Pediatric Neurologist, University of Michigan • Kathy Mathews, MD Director, Division of Pediatric Neurology, Development and Behavior Professor, Departments of Pediatrics and Neurology, University of Iowa Carver College of Medicine, University of Iowa Children’s Hospital • Xiao Xiao, PhD Fred Eshelman Distinguished Professor of Gene Therapy, University of North Carolina, UNC Eshelman School of Pharmacy • Brenda Wong, MD Associate Professor of Clinical Pediatrics and Neurology, Director, Pediatric Neuromuscular Program and MDA Clinic, Cincinnati Children’s Hospital Medical Center • Robert Griggs, MD, FAAN Professor of Neurology, Medicine, Pediatrics Pathology and Laboratory Medicine, University of Rochester School of Medicine, Chair, Muscle Study Group Executive Committee

12. Support • Patient Advocacy Groups • Cure CMD (Congenital Muscular Dystrophy) • Struggle Against Muscular Dystrophy (SAM), Ireland • Muscular Dystrophy Association (MDA) • Parent Project Muscular Dystrophy (PPMDP) • Charley’s Fund, Inc. • Government Organizations • National Institute of Health (NIH) – financial support (3 grants) • Treat-NMD (Neuromuscular Disease), European Union