Abstract Details

Title Results of Testing the First in Class Utrophin Upregulator, SMT C1100, in a Phase 1 Healthy Volunteer Study

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P01 - (-)

Poster/Presentation
Number 119

Objective

Background BACKGROUND: DMD is the most common form of muscular dystrophy and affects approximately 250,000 patients worldwide due to an inability to make dystrophin, resulting in loss of skeletal muscle. During foetal muscle development utrophin takes the functional role of dystrophin, then is gradually replaced by dystrophin as the fibres mature. Continual muscle expression of utrophin can functionally replace dystrophin potentially overcoming the dystrophin deficit in DMD. In animal studies, daily SMT C1100 treatment significantly reduced muscle pathology leading to better muscle function including reduction of muscle fatigue analogous to the 6 minute walk distance test used in patient trials.

Design/Methods DESIGN/METHODS: A Phase 1, double-blind, placebo-controlled study has been completed in healthy male subjects. Each group consisted of six volunteers on drug and two on placebo. The single ascending dose escalated from 50mg/kg to 400mg/kg with the repeat dosing performed at 100mg/kg bid and 200mg/kg bid. The primary objective was safety and tolerability of single and multiple oral doses of SMT C1100 with secondary objectives to determine dose pharmacokinetics of SMT C1100 and determine the effect of food.

Results RESULTS: The aqueous formulation of SMT C1100 was orally delivered and well tolerated with no drug related adverse events apart from some incidence of pale stools at high doses. On repeat dosing with 100mg/kg bid, SMT C1100 plasma concentrations achieved levels in all volunteers above that required to increase utrophin expression by at least 50%.

Conclusions CONCLUSIONS: The data are supportive of SMT C1100 moving into DMD patient trials. This is the first example of a utrophin upregulation therapy to enter the clinic with the potential to treat all DMD patients.

Authors/Disclosures
Jon Tinsley PRESENTER	No disclosure on file
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
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