As reported in Business Wire, Vico Therapeutics has initiated patient dosing in an expanded cohort of its Phase 1/2a clinical study evaluating VO659, an antisense oligonucleotide (ASO) designed to target the CAG repeat expansions that drive Huntington’s disease (HD), spinocerebellar ataxia type 3 (SCA3), and spinocerebellar ataxia type 1 (SCA1). The trial, now incorporating a twice‑annual dosing schedule, is being conducted across several European sites.
A First‑in‑Class Approach to Polyglutamine Disorders
VO659 is currently the only clinical‑stage therapy built to directly engage the pathogenic CAG repeat expansion, a genetic defect responsible for all nine known polyglutamine diseases. The therapy is engineered to preferentially decrease mutant huntingtin (mHTT) protein levels while aiming to maintain expression of the normal HTT protein.
Earlier interim results showed a 38% reduction in cerebrospinal fluid (CSF) mHTT and a 2.5% decrease in CSF neurofilament‑light (Nf‑L) four months after dosing in HD participants—signals that suggest target engagement and a favorable biomarker profile.
Progress in an Extended Dosing Regimen
The ongoing study is assessing safety, tolerability, pharmacokinetics, and pharmacodynamic effects over a 12‑month period using intrathecal administration every six months. Thus far, multiple participants have received VO659 with no serious adverse events reported.
Vico CEO Micah Mackison noted that the early biomarker shifts are encouraging and highlighted that the long half‑life of the drug enables a convenient dosing schedule that may benefit patients if long‑term safety is confirmed.
The European arm of the study is being conducted under an approved Clinical Trial Application (CTA) and is listed on ClinicalTrials.gov under NCT05822908.
U.S. IND Clearance Expands Program
In a parallel advancement, the U.S. Food and Drug Administration has cleared Vico’s Investigational New Drug (IND) application, enabling the company to begin U.S.-based clinical studies later this year. This move broadens the global development footprint for VO659 and positions the program for continued momentum.
New Mechanistic Data Presented at HD Conference
At the CHDI Foundation’s 21st Annual Huntington’s Disease Therapeutics Conference, Vico’s scientific leaders are presenting new findings on VO659’s mechanism of action. According to the company, the ASO not only engages the toxic CAG repeat–containing transcripts but may also modulate several pathways implicated in repeat‑mediated cellular dysfunction. A clinical update from the Phase 1/2 trial is also being shared.
