Slide 1: Resolaris Clinical Program – Data Update
Resolaris Clinical Program – Data Update December 13, 2016 Exhibit 99.3
Slide 2: Resolaris Clinical Program Summary
Resolaris Clinical Program Summary Trial Indication(s) Patients Highest Dose Design Data Timing 002 Adult FSHD 3 dose cohorts (n=20 Total) 3mg/kg weekly Placebo controlled, Double blinded; Interpatient Dose Escalation Announced 1Q 2016 003 Early onset FSHD Stage 1 (n=8) 3mg/kg weekly Open-label, Int
Slide 3: Adult LGMD2B and FSHD (004) Trial Study Design
1mg/kg (biw) 1mg/kg 0.3mg/kg Placebo Adult LGMD2B and FSHD (004) Trial Study Design Objective & Rationale Objective: Evaluate the safety/tolerability of total weekly exposure of 6.0mg/kg in LGMD2B and FSHD Assess drug activity more proximal to dosing Rationale: To evaluate different dosing regimens
Slide 4: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Characteristic Group A FSHD Group B FSHD Group B LBMD2B Enrolled 4 4 10 Age (Mean years) 45.0 34.0 37.2 Median (Range) 45.0 (39, 51) 33.5 (33, 36) 33.5 (22, 62) Male (number, %) 3, 75% 4, 100% 3, 30% White (number, %) 4, 100% 4, 100% 9, 90% BMI (kg/m2), mean
Slide 5: Global Manual Muscle Testing
Global Manual Muscle Testing Muscle function/strength was formally assessed by investigators using Manual Muscle Testing (MMT) 14 muscles evaluated at different time points in studies Muscles scored individually Composite score calculated Progression: lower scores Negative change from baseline Impro
Slide 6: MMT Scores FSHD and LGMD2B (004 Trial)
MMT Scores FSHD and LGMD2B (004 Trial) Individual Patient Changes from Baseline (%) *1-week follow-up is earlier than week 14 for 2 early discontinuations †One patient did not complete the MMT assessments due to being wheel chair bound Dosing up to 3 mg/Kg BIW Dosing up to 1 mg/Kg BIW FSHD/LGMD Clin
Slide 7: Global Patient Reported Outcomes: INQoL
Global Patient Reported Outcomes: INQoL Individualized neuromuscular quality of life assessment * Vincent KA et al: Construction and Validation of a Quality of Life Questionnaire for Neuromuscular Disease (INQoL). Neurology 2007, 68:1051-1057. FDA: “Generally, findings measured by a well-defined and
Slide 8: Overall INQoL Score (004 Trial)
Overall INQoL Score (004 Trial) Individual Change from Baseline FSHD/LGMD Clinical Activity Dosing up to 3 mg/Kg BIW Dosing up to 1 mg/Kg BIW Week 14 INQoL LGMD2B (n=10) Week 14 INQoL FSHD (n=8)
Slide 9: Summary Trial Clinical Activity Assessments
Summary 004 Trial Clinical Activity Assessments FSHD (up to 1.0 mg/kg biw) FSHD (up to 3.0 mg/kg biw) LGMD2B (up to 3.0 mg/kg biw) FSHD (up to 1.0 mg/kg biw) FSHD (up to 3.0 mg/kg biw) LGMD2B (up to 3.0 mg/kg biw) MMT INQoL
Slide 10: Biomarker Evaluation
Biomarker Evaluation 004 Trial 004 Trial included various exploratory biomarkers Exploratory biomarkers did not generally establish sufficiently high or consistent levels or robust signals across a sufficient number of patients to determine test article effects Including targeted muscle T2 and STIR
Slide 11: Early Onset FSHD (003) Trial
3mg/kg 1mg/kg 0.3mg/kg Placebo Early Onset FSHD (003) Trial Objective: Evaluate the safety/tolerability in a potentially different indication Early Onset FSHD Assess drug activity in new patient population and with additional endpoints Rationale: Investigate an often more severe form of disease, inv
Slide 12: Overall MMT Score (003 Trial)
Overall MMT Score (003 Trial) Individual Change from Baseline (%), Per Protocol Pop. Early Onset FSHD Week 14 MMT Early Onset FSHD (n=4)
Slide 13: Overall INQoL Score (003 Trial)
Overall INQoL Score (003 Trial) Individual Change from Baseline, Per Protocol Pop. Early Onset FSHD † One patient did not complete INQoL at baseline Week 14 INQoL Early Onset FSHD (n=3†)
Slide 14: Adult FSHD Long-Term Safety Extension (005) Trial
Adult FSHD Long-Term Safety Extension (005) Trial Evaluate Safety and Tolerability: Build safety dossier for Resolaris Evaluate Potential Activity Assessments: Manual Muscle Test (MMT) Individualized Neuromuscular Quality of Life (INQoL) Biomarker Assessments Patients receive weekly doses of 3.0 mg/
Slide 15: Safety & Tolerability Overview: 003, 004 & 005
As of December 1, 2016, 44 patients have received Resolaris, across all trials (including 002, 003, 004, and 005), for a total drug exposure of 149 patient months Resolaris demonstrated a favorable safety profile and was generally well-tolerated across all doses tested in: Adult FSHD, Early onset FS
Slide 16: Potential Safety & Tolerability Related Protocol Changes
Protocol related discontinuations: Discontinued with a single IRR*(4 FSHD/1 LGMD): all IRRs mild to moderate, transient If Jo-1 Ab unit levels reach cut-off (5 FSHD): without associated clinical symptoms One LGMD patient discontinued from the 004 Trial for non-drug related reasons After changing the
Slide 17: Overall MMT: FSHD, LGMD2B & Placebo
Overall MMT: FSHD, LGMD2B & Placebo Change from baseline at week 14 FSHD/LGMD Activity 004 FSHD 1mg/kg 004 FSHD 3 mg/kg 004 LGMD* 3 mg/kg 002 FSHD 3 mg/kg 002 Placebo 3 mg/kg *One patient in 004 Trial did not have an MMT measurement due to being wheelchair bound 003 E.O. FSHD 3 mg/kg 15/23 patients
Slide 18: Overall INQoL: FSHD, LGMD2B & Placebo
Overall INQoL: FSHD, LGMD2B & Placebo Change from baseline at week 14 FSHD/LGMD Activity 004 FSHD 1mg/kg 004 FSHD 3 mg/kg 004 LGMD 3 mg/kg 002 FSHD 3 mg/kg 002 Placebo 3 mg/kg 003 E.O. FSHD 3 mg/kg 14/23 patients improved or were stable with Resolaris of ≥ 3mg/kg for at least 6 weeks 3/4 patients im