1. Morquio A: Burden of disease

2. Morquio A is a multisystemic disorder Clinical manifestations: • Skeletal dysplasia • Short stature • Cervical spine instability • Spinal cord compression • Impaired endurance • Respiratory disease • Hearing loss • Corneal clouding • Heart valvular disease • Dental abnormalities • Normal intelligence

3. Morquio A is progressive 3 mo 3 yr 7 yr 14 yr 18 yr 26 yr 10 yr 16 yr 17 yr 28 yr 30 yr 4 yr Morquio A disease process leads to progressive multisystemic manifestations

4. Patients typically require surgery > 70% of 325 Morquio A subjects had at least one surgical procedure n = 325 Morquio A subjects (mean age= 14.5 years) Data based on medical history reviews Harmatz et al, Mol Genet Metab, 2013 MorCAP baseline data

5. Mobility is compromised Use of wheelchairs and walking aids is common • MorCAP baseline data (Harmatz et al, 2013) revealed: • 49% of 300 Morquio A subjects required wheelchairs (mean age= 14.5 years) • 26% of 298 Morquio A subjects used walking aids (mean age= 14.5 years) • Data from the International Morquio A Registry (Montano et al, 2007) revealed: • 31% of 326 Morquio A patients needed wheelchairs (mean age = 14.2 ± 11.1 years) • 19% of 326 Morquio A subjects used walking aids (mean age = 14.2 ± 11.1 years) Harmatz et al, Mol Genet Metab, 2013; Montano et al, J Inherit MetabDis, 2007

6. Patients often experience difficulties in activities of daily living • Upper limb abnormalities contribute significantly to • activity limitations • Wrist hypermobility and weak hand grip cause difficulties with tasks requiring strength, such as lifting heavy objects and pouring from a bottle (Aslam et al, 2012) • MorCAP baseline data (Harmatz et al, 2013) revealed limitations in patients’ ability to perform day-to-day tasks • Of the 153 Morquio A subjects ≥ 12 years of age: • 30% could not cut their fingernails • 22% could not tuck in shirts • 22% were unable to open jars • 20% were unable to tie shoelaces Aslam et al, JIMD Rep, 2013; Harmatz et al, Mol Genet Metab, 2013; BioMarin data on file

7. Endurance is impaired Mean 6MWT = 212.6 ±152.2 m (n = 316 subjects) Mean 3MSCT = 30.0 ±24.0 stairs (n= 274 subjects) Mean 6MWT Mean 3MSCT n=215 n=59 n=274 n=248 n=68 n=316 Harmatz et al, Mol Genet Metab, 2013 MorCAP baseline data

8. Patient quality of life declines with disease progression • deteriorating vision, hearing, and oral health • progressive musculoskeletal, cardiac and respiratory impairments • decreasing mobility and endurance • increasing dependence on caregivers In Morquio A, patient quality of life is compromised by: Harmatz et al, Mol Genet Metab, 2013; Hendriksz et al, J Inherit MetabDis, 2012; Montano et al, J Inherit MetabDis, 2007

9. Maximizing functional capacity is the key to optimizing quality of life Optimizing the functional status of major organ systems and, consequently, the quality of life of Morquio A patients requires: • multidisciplinary management • regular assessments • timely interventions • timely post-operative rehabilitation

10. Endurance testing assesses functional capacity Endurance tests measure the efficiency of performing a task and provide assessments of: • Functional status of the cardiac, respiratory and musculoskeletal systems • Overall disease progression • Quality of life • Response to treatments McDonald et al, J PediatrRehabil Med, 2010; Hendriksz et al, J Inherit MetabDis, 2012

11. Submaximal intensity tests are sensitive indicators of endurance for MPS patients Recommended endurance tests for assessing submaximal functional capacity in Morquio A patients include: 6 minute walk test (6MWT) • measures how far a person can walk on a hard, flat surface in 6 minutes • a standardized test (American Thoracic Society, 2002) • used to assess endurance in patients with MPS VI (Harmatz et al, 2005) and Morquio A (Harmatz et al, 2013) 3 minute stair climb (3MSCT) • measures how many steps a person can ascend in 3 minutes, using rails and resting as needed • used to assess edurance in patients with MPS VI (Harmatz et al, 2005) and Morquio A (Harmatz et al, 2013) Image courtesy of Elizabeth Wright Harmatz et al, Mol Genet Metab, 2013; Harmatz et al, Pediatrics, 2005; McDonald et al, J PediatrRehabil Med, 2010; Hendriksz et al, J Inherit MetabDis, 2012

12. Regular assessments are recommended for optimal patient quality of life Hendriksz et al, J Inherit MetabDis, 2012