Polymorph Analysis of ALZ-801 (Valiltramiprosate), a Valine-conjugated Oral Prodrug of Tramiprosate in Late-stage Clinical Development for Alzheimer’s Disease

Abstract ALZ-801 (valiltramiprosate) is an orally bioavailable, small-molecule inhibitor of β-amyloid (Aβ) oligomer formation in late-stage clinical development as a potential disease-modifying treatment for Alzheimer’s disease (AD). ALZ-801, (S)-3-(2-amino-3-methylbutanamido) propane-1-sulfonic acid, is a valine-conjugated prodrug of tramiprosate. Structural, polymorphic analysis of the active pharmaceutical ingredient (API) of ALZ-801 showed extra peaks when high throughput transmission mode XRPD analysis was utilized. After extensive investigation, the extra peaks were determined to be an artifact of transmission mode XRPD, which was not observed in either reflectance or capillary mode XRPD analyses. Reflectance mode XRPD was demonstrated as the most appropriate methodology to monitor the crystal form of ALZ-801 API. In conclusion, ALZ-801 API is a single polymorph form.