| References: |
ALZ-801 is an orally available, valine-conjugated
prodrug of tramiprosate. Tramiprosate, the active
agent, is a small-molecule b-amyloid (Ab) anti-oligomer
and aggregation inhibitor that was evaluated extensively in
preclinical and clinical investigations for the treatment of
Alzheimer’s disease (AD). Tramiprosate has been found to
inhibit b-amyloid oligomer formation by a multi-ligand
enveloping mechanism of action that stabilizes Ab42
monomers, resulting in the inhibition of formation of oligomers
and subsequent aggregation. Although promising
as an AD treatment, tramiprosate exhibited two limiting
deficiencies: high intersubject pharmacokinetic (PK) variability
likely due to extensive gastrointestinal metabolism,
and mild-to-moderate incidence of nausea and vomiting.
To address these, we developed an optimized prodrug,
ALZ-801, which retains the favorable efficacy attributes of
tramiprosate while improving oral PK variability and gastrointestinal
tolerability. In this study, we summarize the
phase I bridging program to evaluate the safety, tolerability
and PK for ALZ-801 after single and multiple rising dose
administration in healthy volunteers. |
