PRI-002: An Investigational Oral Peptide for Early Alzheimer's Disease

I. Executive Summary

PRI-002 is an investigational therapeutic agent, administered orally as an all-D-enantiomeric peptide, currently under development for the treatment of early-stage Alzheimer's disease (AD), encompassing Mild Cognitive Impairment (MCI) and mild dementia attributable to AD. The compound's purported mechanism of action is novel, centering on the direct, chaperone-like disassembly of toxic, self-replicating amyloid-beta (Aβ) oligomers into their constituent, putatively harmless Aβ monomers. This process is described as possessing anti-prionic characteristics and represents a departure from conventional amyloid-targeting strategies.[1]

Preclinical investigations across multiple animal models reportedly demonstrated a reversal of cognitive deficits. Subsequent Phase 1 clinical trials in healthy volunteers established a satisfactory safety profile and predictable pharmacokinetic parameters. A Phase 1b study involving patients with MCI or mild AD indicated that PRI-002 was well-tolerated, with no significant safety concerns, notably an absence of Amyloid-Related Imaging Abnormalities (ARIA). Furthermore, this trial reported a statistically significant improvement in short-term memory, as assessed by the CERAD word list, at day 56 in the treatment group compared to placebo. However, no significant alterations in cerebrospinal fluid (CSF) biomarkers were observed following 28 days of treatment.[1]