Top-line results from Probiodrug's PQ912 Phase 1 SAD, MAD study for Alzheimer's disease

Probiodrug AG (Probiodrug), a biotech company developing products for the treatment of neurodegenerative and inflammatory diseases, with a particular focus on Alzheimer's disease (AD), today announced top-line results of its Phase 1 single (SAD) and multiple ascending dose (MAD) study of PQ912 in healthy volunteers. PQ912 is a glutaminyl cyclase (QC) inhibitor for the treatment of AD and it is the first QC inhibitor to enter clinical development.  

The Phase 1 trial, conducted in Switzerland, demonstrated that PQ912 is safe and well tolerated after oral dosing. Dose-proportional pharmacokinetics and a strong pharmacokinetic and pharmacodynamic relationship based on QC inhibition were observed in plasma and cerebrospinal fluid. The combined SAD/MAD study involved 100 volunteers in a blinded, placebo controlled randomized trial.  

PQ912 is a small molecule that targets QC, an enzyme that catalyzes the formation pyroGlu amyloid-beta (A-Beta) a highly toxic A-Beta variant that is involved in the development and progression of AD. AD is a neurodegenerative disease characterized by deposits of extracellular A-Beta plaques in the brain, intraneuronal tangles and cerebral neuronal loss. QC inhibitors address a major pathology associated with AD by inhibiting the formation of A-Beta variants which lead to the assembly of highly neurotoxic A-Beta-oligomers.

"This first in human study of PQ912 is a significant milestone for Probiodrug, creating a compelling data package that will enable further clinical development in AD," commented Dr. Konrad Glund, chief executive officer of Probiodrug. "We look forward to presenting the full data set from this study at an upcoming conference."

Prof. Dr. Hans-Ulrich Demuth, CSO of Probiodrug added, "The study provides us the platform that will lead to the generation of first clinical evidence from future Phase 2 studies in patients to support QC inhibition as a promising and innovative approach to treat Alzheimer's disease."  Data from preclinical studies published in Nature Medicine have shown that QC inhibitors in vivo effectively block the production of pyroglutamate-modified A-Beta, a highly neurotoxic A-Beta variant, and to prevent the aggregation of all types of A-Beta in the brain. The data also demonstrate that QC inhibitors are able to reduce neurotoxicity, neuroinflammation and restore cognitive function in preclinical models of AD.

SOURCE Probiodrug AG