S127 pre-mRNA splicing modifier that increases the levels of functional SMN protein. Jewelfish (NCT03032172) is a multicenter, open-label study of daily oral risdiplam in non-naïve patients with SMA, aged 6 months to 60 years. Jewelfish participants previously received RG7800 (RO6885247), nusinersen (SPINRAZA R), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA R). Jewelfish (N = 174) assesses the safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD) relationship of risdiplam. We have previously presented safety data from 45 patients with SMA (datacut: 28th June 2019) who received risdiplam for up to 28.9 months (nine patients previously received RG7800, 24 patients received nusinersen and 12 patients received olesoxime). No drug-related safety findings leading to withdrawal were reported and there have been no treatment-related safety findings leading to withdrawal in any risdiplam trial (data-cut: 28th June 2019). In an earlier analysis of SMN protein in whole blood from patients in Jewelfish, while patient numbers were limited (n = 18), the magnitude of SMN protein increase (> 2-fold) was comparable to that in SUNFISH Part 1 (NCT02908685) in patients with Types 2 and 3 SMA who had not previously received an SMN2-targeting therapy. We will present updated data on safety and PK/PD from patients within the Jewelfish study, including new patients, and reasons for discontinuing previous treatment regimens. The Jewelfish study is ongoing in sites across Europe and the US.