Cure CMD 2010 CMD Family Conference Mission & Goals Roadmap Treatment

Mission To raise CMD awareness and identify treatments for the CMDs The men who build the future are those who know that greater things are yet to come, and that they themselves will help bring them about. Their minds are illuminated by the blazing sun of hope. They never stop to doubt. They haven’t time. ~Micheal Egan

Cure CMD Mission Treat/Cure Fund and Focus Research Biospecimen Repository Animal Model and Cell systems HTS Drug Pipeline

Cure CMD Goals: Discover Fundraise Treat

Goal 1: Discover CMD GoalTask CMDIRRegister global population CMD New GenesIdentify CMD Diagnostic Guidelines Publish and distribute BiomarkersFind and validate Natural HistoryLaunch CMD ResearchFund CMD BioBankDonate and grow

CMDIR Recently endorsed by AFM, Muscular Dystrophy Campaign (UK), Muscular Dystrophy Australia 23 countries represented Translated into: Portuguese, Spanish, German, French, English (Danish and Turkish forthcoming) Global registration= Power in Numbers and a Genetically Characterized Population

CMD New Genes Ongoing international effort to identify new genes with a particular focus on: a. Collagen VI like picture without collagen VI Mutation b. Dystroglycanopathy without 1/6 known gene mutations identified New Genes= New Targets

CMD Diagnostic Guidelines CMD Standard of Care Committee, Brussels, Nov CMD Care Guidelines 2. CMD Diagnostic Guideline Cure CMD is working with Dr. Sparks and Dr. Susana Quijano Roy to revise Genetest Diagnostic Guidelines= Recognition, Less Diagnostic Odyssey, Increased Rates of Genetic Confirmation of CMD community

CMD Biomarkers A biomarker is “something” you find in the blood, urine or muscle or on imaging that helps you track or mark disease progression OR improvement Biomarkers help a doctor monitor a disease Biomarkers help a scientist tell if a drug is working Biomarkers help confirm if a person who is treated says they feel stronger that there is a positive effect at the muscle level Biomarkers can given information about rate of disease progression Biomarkers can help a doctor titrate medication dose Biomarkers= Showing an Effect or Rate of Disease Progression on a Cellular or Organ System Level

CMD Natural History Follow people with CMD over time, looking at biomarkers, outcome measures and imaging To lead to this: CMD Translational Grant: Jim Collins, Biomarkers, Jan 2010 CMD Quality of Life Survey, March 2010 ENMC CMD Outcome Measure Meeting, March 2010 CMD Comparative Outcome Measure study, June 2010 NINDS and CMD: Common Data Elements Meeting, Sept 2010 CMD Motor Outcome Measure Meeting, October 2010 Natural History Study=Validation of Outcome Measures, Increases Ability to Measure Drug Effect

CMD Research Partnered with SAM in 2009 to fund >200K in CMD Research CMD Scientific Conferences: July 2009 Therapeutic Targets in the CMDs Jan 2010 CMD High Throughput Screening, NCGC Cure CMD SMAB, Sept 2010 Evaluate critical needs, direction and funding priorities Funding Research=Power to Identify and Evaluate Future Targets

Goal 2: TREAT CMD GoalTask CMD Care Guidelines Publish and distribute CMD Lay Guidelines Develop and Distribute Types of CMDDevelop video library Pulmonary care Develop video library

Goal 3: Fundraise CMD CanMakeDonation

Upcoming Events Tully’s Run for Owen, August 21, 2010 Cure CMD Team ~San Jose Rock N Roll ½ Marathon, October 3, 2010 Rage Against the Disease Art Auction, October 10, 2010 Cure CMD Team~Los Angeles Rock N Roll ½ Marathon, October 24, 2010 Cure CMD Team ~Long Branch ½ Marathon, May 1 st, 2011

Mission & Goals Roadmap Treatment

Stay on Mission, Build the Community, Prepare for clinical trials Family CMDIR CMD Family Conference CMD Lay Guidelines Scientist Annual Scientific Meetings Fund Translational Research Animal models, Biomarkers CMD BioBank Clinician SOC Care Guidelines Outcome Measures Biomarkers

Manage a Roadmap Preclinical Trials Clinical Trials What target? What endpoints? What delivery system? How big is the effect? What preliminary data? Combination therapy? What validation workflow?

CMD Target Roadmap Drug or Mechanism Preclinical: HTS animal model Valley of Death: funding toxicology preclinical studies drug manufacture Clinical Trials: funding Laminin 111 X X Omigapil X X N- Acetylcysteine X X IPLEX/IgF X Upregulation glycosylation X Upregulation CT Gal NAC transferase activity X

Clinical Trial Readiness Clinical Trials Natural History StudyBiomarkers Outcome Measures Defined patient cohorts Refine clinical trial design

Clinical Trials Holy grail is not clinical trials, it is a treatment that works. To objectively determine a treatment works, we go through clinical trials. Right drug, right population. We cannot afford a major learning experience at the clinical trial level.

Treatments Clinical Trial Readiness Collaborations Roadmap