Netherlands-based clinical-stage genetic medicines company Vico Therapeutics BV announced on Friday that it had revealed new positive interim data in Huntington's disease (HD) from the ongoing Phase 1/2a clinical trial of VO659, an investigational allele-preferential antisense oligonucleotide (ASO) therapy, at an oral presentation at the European Huntington's Disease Network's EHDN & Enroll-HD 2024 meeting on 13 September.

This is the first clinical data reported for VO659, which is designed to target the CAG repeat expansion that causes all nine known polyglutamine diseases, including HD as well as spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3). VO659 has a unique allele-preferential mechanism of action that targets expanded CAG repeats in the mutant mRNA transcript and inhibits mRNA translation leading to a reduction of mutant protein, with the potential to halt or slow disease progression. VO659 is the only clinical-stage program that directly targets the underlying CAG repeat expansion that causes HD.

The Phase 1/2a clinical trial is a multi-centre, open-label, multiple ascending dose study designed to assess the safety and tolerability of four doses of VO659 administered intrathecally every four weeks in participants with early manifest HD, or mild to moderate SCA1 or SCA3. Exploratory endpoints include the assessment of pharmacodynamic (PD) biomarkers (mHTT, mATXN3 and Nf-L protein) in cerebrospinal fluid (CSF), pharmacokinetics in CSF and plasma and clinical outcome measures. The interim analysis provides a look at available safety, tolerability and PD data for HD participants in the 40mg cohort until at least day 85 of the study.

Micah Mackison, Vico CEO said that the first data from our Phase 1/2a clinical trial of VO659 in participants living with HD is highly encouraging as we saw immediate reductions in CSF mHTT and no changes in Nf-L protein, two key biomarkers in HD, in treated patients over the available follow-up period. Given VO659's long anticipated half-life, there is clear potential for this therapy to have an infrequent dosing schedule and we look forward to exploring this further in clinical trials.