A Study to Assess the Efficacy and Safety of IONIS-SMN Rx in Infants With Spinal Muscular Atrophy

This is a Phase 3 multicenter, double-blind, randomized, sham-procedure controlled study of
IONIS-SMN Rx in patients with infantile-onset SMA. Subjects will be randomized 2:1 to
receive IONIS-SMN Rx or a sham procedure control, respectively.

Inclusion Criteria:

- Be 7 months (210 days) of age or younger at screening

- Be born (gestational age) between 37 and 42 weeks

- Be medically diagnosed with spinal muscular atrophy (SMA)

- Have SMN2 Copy # of 2

- Body weight equal to or greater than 3rd percentile for age using appropriate
country-specific guidelines

- Be able to follow all study procedures

- Reside within 9 hours ground travel each way, for the duration of the study

- Meet additional study-related criteria

Exclusion Criteria:

- Hypoxemia (O2 saturation awake less than 96% or O2 saturation asleep less than 96%,
without ventilation support) during screening evaluation

- Meet additional study-related criteria