Sanjay Bidichandani, MBBS, PhD Vice President for Research Basic Research Target Identification Drug Screening “Proof-of-Principle” Testing in Animals Translational Research “Preclinical Drug Development” Clinical Research Including Trials

MDA’s Research Portfolio Total ~300 grants~$100 M Annually~100 new grants~$40 M Medical Advisory Committee Scientific Advisory Committee Translational Res Advisory Committee Ad hoc peer-review

Muscular Dystrophies Duchenne Becker Limb-Girdle Facioscapulohumeral Congenital Oculopharyngeal Distal Emery-Dreifuss Myotonic dystrophy Metabolic Myopathies Phosphorylase Deficiency Acid Maltase Disease Phosphofructokinase Deficiency Debrancher Enzyme Deficiency Mitochondrial Myopathy Carnitine Deficiency Carnitine Palmityl Transferase Deficiency Phosphoglycerate Kinase Deficiency Phosphoglycerate Mutase Deficiency Lactate Dehydrogenase Deficiency Myoadenylate Deaminase Deficiency Other Myopathies Myotonia Congenita Paramyotonia Congenita Central Core Disease Nemaline Myopathy Myotubular Myopathy Periodic Paralysis Motor Neuron Disease Amyotrophic Lateral Sclerosis Spinal Muscular Atrophy Spinal Bulbar Muscular Atrophy Inflammatory Myopathies Polymyositis Dermatomyositis Inclusion Body Myositis Neuromuscular Junction Diseases Myasthenia Gravis Lambert-Eaton Syndrome Congenital Myasthenic Syndromes Endocrine Myopathies Hyperthyroid Myopathy Hyopthyroid Myopathy Diseases of Peripheral Nerve Charcot-Marie-Tooth Disease Friedreich Ataxia Dejerine-Sottas Disease MDA’s Research Portfolio

Active projects (million) Basic Research Drug Screening Target Identification “Proof-of-Principle” Testing in Animals Translational Research “Preclinical Drug Development” Clinical Research Including Trials Basic Research Program Translational / Basic Research Program Translational Translational / other $60.8 $4.8 $14.2 $3.7 $7.2 MDA’s Research Portfolio

FY10 / non-ARRA **

Turning Research into Treatments MDA VENTURE PHILANTHROPY

Target ID Hit ID Lead Optim. Can Pre- IND P1 P2 P3 Reg 2 yrs1yr1.5-2yrs1 yr1 yr 2 yr 2-3 yrs Risk Cost MDA Academia Biotech Big Pharma Translational research MDA’s Drug Development Program

MDA’s Recent Advances In Therapy Development Repligen Friedreich ataxia Repligen Askelepios Duchenne / Becker ReveraGenDuchenne / Becker Duchenne PTC Mendell LGMD2d Miller ALS (SOD1) PoC PreC I/IIa IIb Repligen SMA

“It’s a great time to be a mouse with a neuromuscular disease!” John Porter, Ph.D. (NIH / NINDS) …and that’s a good thing…

Challenges How to safely and effectively extend these successes to humans? Who is going to fill the void between biotechs funded by foundations & fed - and - big pharma?

Smart partnership….

Finding Treatments: Smart Partnership Leveraging through MDA’s drug development program Federal govt & other non-profits Partnership with Pharma and Biotech companies Venture capitalists

Enhancing Research through Communication & Collaboration

MDA Neuron Symposium Role of glia in motor neuron degeneration in ALS MDA Muscle Symposium Newborn screening for Duchenne muscular dystrophy MDA Translational Symposia Encouraging technology transfer from academia Gene therapy for neuromuscular disease (with AFM) MDA Symposium Series

Getting a head start…

MDA Clinic MDA ALS Clinic Duchenne research network ALS research network Clinics & Clinical Research Networks

Currently = 40 Trainees (~$7 million) Historically = 377 trainees (~ $48 million) Investment in Training Researchers…. Basic researchers (DG) Clinical researchers (CRTG)

MVP: Program Review Zero trainees in translational projects!

Bridge to Industry (B2I) B2I postdoctoral fellowships  Training future NMD translational researchers Academia Industry

Future Muscle Disease Researchers