AI Therapeutics sprung into the drug development landscape for amyotrophic lateral sclerosis (ALS) with promising results from a small trial.

The Guilford, Connecticut-based biotech announced that its candidate AIT-101 demonstrated target engagement in a Phase IIa study (NCT05163886) in 14 adults with C9ORF72-associated ALS (C9ALS). Repeat expansions of the gene C9ORF72 are thought to be a leading cause of both ALS and frontotemporal dementia.

In the trial, AIT-101 caused a 73% reduction in the protein aggregate poly(GP)—a biomarker associated with neurodegeneration in C9ALS. AI Therapeutics also reported that AIT-101 met its primary endpoint of safety and increased another AIT-101 biomarker called sGPNMB.

The Phase IIa trial began with a 12-week treatment period where patients were randomized 2:1 to AIT-101 or placebo, followed by an additional 12-week open-label extensions. Patients also had the opportunity to continue into a long-term extension trial that remains ongoing.

AI Therapeutics also reported new preclinical data suggesting AIT-101 could demonstrate therapeutic effects across multiple forms of ALS.

AI Therapeutics plans to submit detailed Phase IIa data for peer-reviewed publication and a future medical conference, though the company is yet to announce the next steps in AIT-101 development for ALS.

AIT-101, previously known as LAM-002A, inhibits the lipid kinase PIKfyve, which could clear toxic protein aggregates in motor neurons.

AIT-101 was previously under investigation in a Phase II trial for Covid-19 (NCT04446377), although there are no results available. The drug was also available through an expanded access program in frontotemporal dementia (NCT05483322).

Advances in biomarkers for ALS

The Phase IIa trial focused on ALS biomarkers, which has become an increasingly common trend in the drug development space. Just last month, FDA Advisory Committee (AdCom) panelists recommended accelerated approval for Biogen’s ALS drug tofersen based on its effect on the biomarker plasma neurofilament.

Meanwhile, major ALS players like BrainStorm Cell Therapeutics have worked on developing ALS genetic biomarkers to predict efficacy in specific patient populations. A future FDA AdCom meeting is also on the books for BrainStorm’s ALS therapy NurOwn.

As for AI Therapeutics, all eyes will be on the company’s future drug development plans in ALS.