Wave Life Sciences Ltd (NASDAQ:WVE) announced results from its Phase 1b/2a SELECT-HD trial of WVE-003, which is being developed as a potential disease-modifying therapeutic for Huntington’s disease (HD).

WVE-003 is designed to lower mutant huntingtin (mHTT) protein and preserve healthy, wild-type huntingtin (wtHTT) protein.

In the multidose portion of the SELECT-HD study (n=23), participants received either every-eight-week (Q8W) intrathecal doses of 30 mg WVE-003 (n=16) or placebo (n=7), with 12 weeks of follow-up.

Key results are as follows:

WVE-003 was generally safe and well-tolerated, with no Serious Adverse Events (SAEs) reported; ventricular volume was in line with natural history.
Significant mHTT protein lowering was observed throughout the 28-week assessment period.
- At 24 weeks (8 weeks after the last dose), mean mHTT lowering in cerebrospinal fluid (CSF) was 46% versus placebo (p=0.0007).
- At 28 weeks (12 weeks after the last dose), mean mHTT lowering in CSF was 44% versus placebo (p=0.0002), which supports quarterly or less frequent dosing.
wtHTT protein was preserved throughout the 28-week assessment period, validating allele-selective silencing. Additionally, statistically significant increases were observed in wtHTT protein versus placebo.
- wtHTT protein supports the health and function of neurons and is crucial for CSF flow in the ventricles.
- mHTT also has a detrimental effect on wtHTT at the protein level, further decreasing its function. Only selective lowering of mHTT can potentially relieve its negative impact on wtHTT protein function.
Most WVE-003-treated participants had neurofilament light protein (NfL) levels that were in the range of placebo or had NfL levels that increased and returned to the range of placebo.
At 24 weeks (the last MRI assessment), mHTT reduction was correlated with slowing of caudate atrophy (R=-0.50; p=0.047). Caudate atrophy is an imaging biomarker predictive of clinical outcomes, including clinically meaningful worsening of Total Motor Score (TMS).
A slowing of decline was observed for TMS for WVE-003 versus placebo (4.25 mean difference at 24 weeks, p=not significant).

Wave expects that its current cash and cash equivalents of $181 million will be sufficient to fund operations into the fourth quarter of 2025.

Price Action: WVE shares traded down 3.07% at $5.05 at last check Tuesday.

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