Therapeutics for the Muscular Dystrophies

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

SAM

Human LAM-111

No LAM-111

Merosin Deficient (MDC1A) mouse treated with laminin-111 (10mg LAM-111/kg/week starting at 10 days of age)

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

Adelina

Industry Science

Drug Development Program

AdvocacyGovernment

Drug manufacture

Animal testing

Clinical testing

Project coordination

Investment

Development incentives

Funding support

Regulatory guidance

Rare Disease Program (HTS

etc)

Preclinical models

Natural history

Patient identification and

accrual

Investment

Patient referral

Trial promotion

Investment

Maia

Aubrey

Philip

3 in 5 Phase III Trials Succeed

* Data from Pharma drugs developed entirely in-house

Adams CP, Brantner VV (2010) “Spending on New Drug Development” Health Econ. 19: 130–141 (2010)

Only 1 in 13Candidates Succeed

Pierce

*LifeSciences World 10/13/2006

Phase I: About $15K/personPhase II: About $19K/personPhase III: About $26K/person

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

Jake

– 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, BiozentrumUniversity of Basel

– Steve D Hauschka, PhD Professor of Biochemistry, University of Washington

– 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, BiozentrumUniversity of Basel

– Steve D Hauschka, PhD Professor of Biochemistry, University of Washington

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Kyra

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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

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

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