Objective: To report exploratory analyses of biomarker and clinical outcomes from a first-in-human study of NIO752 in progressive supranuclear palsy (PSP) and provide rationale for further studies of NIO752 in primary tauopathies.

Background: PSP, a rapidly progressing neurodegenerative movement disorder with no available disease-modifying treatments, is believed to be driven by aggregation of pathological tau species in the central nervous system. NIO752, an antisense oligonucleotide designed to lower synthesis of all tau species, may slow the accrual of tau burden and progression of disability.

Method: The phase 1, placebo-controlled, multiple dose–escalation study (NCT04539041) enrolled participants with probable PSP Richardson syndrome diagnosed <5 years ago and with a Progressive Supranuclear Palsy Rating Scale (PSPRS) score of <40 at screening. Participants received a total of 4 intrathecal injections of NIO752 or placebo (monthly in cohorts 1–4 or every 3 months in cohort 5). The primary endpoint was safety/tolerability (data presented previously). Other endpoints included measures of biomarkers of target engagement (cerebrospinal fluid [CSF] total tau and phosphorylated tau protein 181), an axonal injury marker (CSF and plasma neurofilament light chain), volumetric magnetic resonance imaging (MRI), and disease severity scores.

Results: CSF and plasma biomarker and volumetric MRI measures, as well as longitudinal effects of NIO752 on PSPRS scores, will be presented for participants in the largest cohort (cohort 5; n=33), who received intrathecal NIO752 or placebo every 3 months over a period of 1 year.

Conclusion: Combined evidence of sustained target engagement, an acceptable safety and tolerability profile, and the effects of NIO752 on exploratory outcomes warrant further investigation of this potential treatment in PSP and other primary tauopathies. A pivotal phase 3 randomized, double-blind, placebo-controlled study will further evaluate the efficacy and safety of NIO752 in PSP. Additionally, a phase 2 basket trial will evaluate the safety, tolerability, and pharmacodynamic effects of NIO752 in other primary tauopathies.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/exploratory-results-from-a-phase-1-study-of-nio752-in-progressive-supranuclear-palsy-supporting-further-clinical-studies/