Salanersen (BIIB115) is an investigational, intrathecally administered antisense oligonucleotide with novel modification to the backbone and similar mechanism of action, but higher potency, than nusinersen in nonclinical studies, enabling the potential to maximize clinical outcomes with dosing only once yearly. This Phase 1 study (NCT05575011/EU CT 2023-505643-39) is evaluating the safety/tolerability, pharmacokinetics, and exploratory efficacy of salanersen. Part B evaluates open-label salanersen (40 mg or 80 mg doses) in pediatric participants (aged 0.5–12 years) with spinal muscular atrophy (SMA) previously treated with onasemnogene abeparvovec with suboptimal clinical status. Study objectives are to evaluate the safety/tolerability (primary) and pharmacokinetics (secondary) of salanersen. Exploratory objectives include assessment of neurofilament levels, World Health Organization (WHO) motor milestones, and motor function scales. An interim analysis was performed once the older participants in the 40 mg dose cohort (n = 8) had completed at least 1 year of follow-up. Salanersen was generally well tolerated at the 40 mg and 80 mg dose levels. In participants with elevated baseline plasma neurofilament levels, salanersen treatment was associated with a 70% reduction by Day 180, which was sustained over time. Of the 8 participants with 1-year follow-up available, 4 (50%) achieved new WHO motor milestones beyond what would be expected based on baseline functional status and time on previous treatment, and clinically meaningful improvements were observed on Hammersmith Functional Motor Scale – Expanded (mean +3.3-point improvement) and Revised Upper Limb Module (mean +5.3-point improvement). The interim results of this study will inform the design of planned registrational trials in SMA. Updated interim analyses from the November 2025 data cut will be presented.