Researchers in Life Sciences wave‘ Phase Ib/IIa study of a potential treatment for amyotrophic lateral sclerosis (ALS) shared a positive update on the disease-targeting capabilities of the drug.

The ongoing FOCUS-C9 trial has shown that WVE-004, the clinical candidate for ALS-C9 and frontotemporal dementia (C9-FTD), remained effective at the different doses tested. Participants received doses of 10 mg, 30 mg, and 60 mg for approximately three months and demonstrated clinically significant reductions in poly(GP) counts. After administration of single 30 mg doses, patients showed a 34% decrease in poly(GP) by day 85.

Of the society shares rose 29.6% on the NASDAQ shortly after the announcement.

FOCUS-C9 is an adaptive study designed to determine the dose level and frequency of WVE-004 based on indicators of early engagement. The latest update is based primarily on observations of repeat dipeptide poly(GP) proteins found in cerebrospinal fluid. Poly(GP) is a key biomarker of C9-ALS and C9-FTD. When at lower levels in CSF, it means WVE-004 is engaging with the disease target in the spinal cord and brain.

“While early, these data are encouraging and open up an opportunity to target the disease at the RNA level. It is encouraging to see the benefits of the adaptive study design, where this early analysis has already helped reduce explored doses and enabled more precise analyses, real-time exploration of dose-response and optimization,” commented Merit Cudkowicz, MD, Chief of the Department of Neurology and Director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and chair of the clinical advisory committee for the trial.

A multi-dose cohort aiming to give patients 10 mg per month is in preparation. More single-dose and multi-dose data are also expected to be shared throughout 2022. Wave hopes more positive results will arrive to enable discussions with regulatory authorities on its next development plans.

“Based on our preclinical PK/PD modeling, we expected that relatively low doses would engage [the] target; however, seeing this level of poly(GP) precipitation three months after a single 30 mg dose exceeded our expectations and we expect poly(GP) to decline further with repeated administrations. The next step is to identify a regimen that maximizes reversal with repeat dosing, while potentially allowing quarterly or less frequent dosing,” added Michael Panzara, MD, MPH, Chief Medical Officer and Head of the Discovery Unit and of Wave’s therapeutic development in the same announcement. .

In addition to WVE-004, Wave is moving forward with two PhaseIb/IIa clinical trials of WVE-003 and WVE-N531 in 2022. WVE-003 is a drug that targets SNP3 in Huntington’s disease and will be evaluated in the SELECT-HD study, while WVE-N531 targets exon 53 in Duchenne muscular dystrophy. The company is also working to advance its alpha-1 antitrypsin deficiency program, which utilizes its novel GalNAc-conjugated A-to-I(G) RNA base-editing oligonucleotides. Wave plans to begin studies in the third quarter of 2022.