In six participants who received 6.8 mg/kg Q8W z-basivarsen in the MAD portion, substantial knockdown of DMPK RNA levels and improvement in splicing were noted as early as 3 months post-treatment. Improvement in myotonia, measured by video hand opening time, was also noted at 3 months and sustained through 12 months of treatment. Sustained improvement was observed across multiple measures of muscle strength and function at 12 months, including Quantitative Muscle Testing (QMT) total score, 10-meter walk/run test, 5 times sit-to-stand, and 9-hole peg test. Improvements were noted in QMT scores across both the upper and lower extremities. Clinical meaningfulness of improvements observed with z-basivarsen was supported by patient-reported outcomes measured by the myotonic dystrophy health index total score, as well as subdomains that assess CNS manifestations, mobility, ability to do activities, and upper extremity function. Improvements from baseline were also noted in both patient and clinician impressions of global function. As of April 23, 2025, z-basivarsen has demonstrated a favorable safety profile, with no serious related TEAEs.