An Open-label Safety and Tolerability Study of IONIS SMNRx in Patients With Spinal Muscular Atrophy Who Previously Participated in IONIS SMNRx-CS2 or IONIS SMNRx-CS10

This study will test the safety, tolerability, and pharmacokinetics of multiple doses of
IONIS-SMNRx administered as an intrathecal injection. Multiple doses will be studied in
patients with Spinal Muscular Atrophy, who previously participated in IONIS 396443-CS2 or
IONIS 396443-CS10, and all patients will receive active drug.

Inclusion Criteria:

- Clinical signs attributable to Spinal Muscular Atrophy

- Satisfactory completion of dosing and all study visits in IONIS 396443-CS2 or IONIS
396443 CS10 with an acceptable safety profile, per Investigator judgement.

- Able to complete all study procedures, measurements and visits and parent/patient has
adequately supportive psychosocial circumstances, in the opinion of the investigator

- Estimated life expectancy > 2 years from Screening

- Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use
is planned for study procedure

Exclusion Criteria:

- Have any new or worsening of existing condition which in the opinion of the
Investigator would make the subject unsuitable for enrollment, or could interfere
with the subject participating in or completing the study.

- Dosing in IONIS 396443-CS2 or IONIS 396443-CS10 within 180 days (6 months) of
screening, or longer ago than 396 days (13 months) from screening

- Hospitalization for surgery (i.e. scoliosis surgery) or pulmonary event within 2
months of screening or planned during the duration of the study

- Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy

- Clinically significant abnormalities in hematology or clinical chemistry parameters

- Treatment with another investigational drug, biological agent, or device within
1-month of Screening or 5 half-lives of study agent, whichever is longer. Any history
of gene therapy or cell transplantation.