A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam

In this study, researchers will learn more about the effects and safety of BIIB115, also known as salanersen.

Specifically, researchers will learn more about how salanersen works in individuals with SMA who are between the ages of 15 and 60 years old. In most people living with SMA, changes to or a lack of a gene called survival motor neuron 1 (SMN1) - often referred to as gene mutations or variants - affect how this gene works. As a result, their bodies produce less SMN protein. Without enough of this protein, motor neurons and muscles cannot work properly. There is a similar gene called SMN2 that produces SMN protein, but it usually does not produce enough SMN protein on its own to make up for the changes in the SMN1 gene. Salanersen is a drug designed to help the SMN2 gene to make more working SMN protein.

In this study, there will be 2 groups of participants: a group who has never received treatment for SMA before joining this study, and a group who has been treated with risdiplam, an approved drug for SMA . Those participants must not have received any other SMA treatments before and will need to stop their risdiplam treatment for the duration of the study.

The main goal of this study is to learn more about how salanersen affects the participants' motor function. Researchers will use different tests and questionnaires to learn if motor function is changing over the study duration.

The main question researchers want to answer in this study is:

• For the group who has never been treated for SMA, how much do scores on the HFMSE movement test change at 12 months compared to the beginning of the study? The Hammersmith Functional Motor Scale - Expanded (HFMSE) has 33 activities that are scored which include sitting, lying down, walking, jumping, and more.

Researchers will also learn more about:

• The effects on participants' motor function and how well their nerves and muscles function.
• The effects on participants' overall sense of change and how they perform daily activities.
• How many participants have adverse events or serious adverse events. Adverse events are health problems that may or may not be caused by the study drug.
• How much salanersen gets into the fluid surrounding the brain and spinal cord.
• How much salanersen gets into the blood.

This study will be done as follows:

• First, participants will be screened to check if they can join the study. The screening period may be up to 4 weeks.
• This is an "open-label" study. This is a study in which the participants, study doctor, and site staff will know that participants are receiving salanersen.
• All participants will receive salanersen through an intrathecal injection, or one that is given into the fluid surrounding the brain and spinal cord.
• Participants will receive salanersen once every year for a total of 5 times throughout the study.
• Including screening, participants will have 17 study visits and 9 telephone calls during this study, which will last up to 61 months in total.