An Expanded Access Protocol of Intravenous Trehalose Injection 90 mg/mL Treatment of Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative. There are two FDA-approved medications to slow ALS progression, riluzole and edaravone; their effect is modest, but additive given that they target different biological pathways. Additional pathophysiologic pathways can be targeted to provide even more additive effect. Autophagy is

dysregulated in ALS and is a promising target for novel therapeutic development. Trehalose (SLS-005, Seelos Therapeutics) is a disaccharide that is well known for its ability to activate autophagy. Three in vivo studies demonstrated a protective effect in SOD1 mouse models (G93T and G86R). In humans, trehalase breaks down trehalose in the gut, so it must be

delivered intravenously (IV) to preserve its effect. The safety and efficacy of trehalose are currently being tested in the HEALEY ALS Platform Trial. The trial design includes an efficacy randomized controlled trial (RCT) followed by an open label extension (OLE). In the trial, participants undergo weekly IV infusions of trehalose, which

are done either at the center or at home by a trained infusion nurse. Unfortunately, the trehalose OLE will end for most participants before the results of the RCT are known due to financial constraints as Seelos is a small business. For the same reason, expanded access is not currently available to people who are not eligible for the RCT.

The current proposal is an expanded access protocol (EAP) of trehalose that will include both people who are not eligible for clinical trials (Cohort 1) as well as people who completed their participation in the trehalose OLE of the HEALEY ALS Platform Trial and are no longer eligible for participation in other trials (Cohort 2). The latter group will be exposed for an additional six

months. Outcome measures for this EAP will include safety, the biofluid biomarker neurofilament light (NFL), clinical measures of disease progression, and survival. This study will provide real- world data to supplement the trehalose clinical development program by evaluating the effects of the drug in a population that is broader than the one included in the RCT and by

collecting outcomes over longer term exposure. Data will be collected in format that can be submitted to FDA and could therefore be included in a potential NDA submission.