Prothena announces new data from PRX012 program for Alzheimer’s disease

Prothena announced new preclinical data from its PRX012 program, a potential best-in-class anti-amyloid beta, or Abeta, product candidate in development for the treatment of Alzheimer’s disease, at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Gothenburg, Sweden. To build a more in-depth understanding of the profile of PRX012 and its potential as an anti-Abeta treatment for Alzheimer’s disease, two preclinical studies presented in an oral presentation at AD/PD 2023 compare a PRX012-surrogate to approved and investigational molecules. Surface Plasmon Resonance was used to compare PRX012s to lecanemab+ and showed that PRX012s had approximately 20-fold higher affinity to Abeta protofibrils as compared to lecanemab when tested under the same conditions. This result was largely driven by a slower binding dissociation rate of PRX012s versus lecanemab. The second study, an ex vivo study using post-mortem Alzheimer’s disease brain tissue, was designed to test the ability of PRX012s to clear pyroglutamate-modified Abeta deposited in plaques. Study results showed that lower concentrations of PRX012s induced more potent and robust clearance of pyroglutamate-modified Abeta as compared to donanemab+. In the experiment, microglia simultaneously phagocytosed non-pyroglutamate-modified Abeta and pyroglutamate-modified Abeta in the presence of PRX012s, indicating that high opsonization efficiency of plaques by PRX012s was sufficient to clear both forms of Abeta. These data add to the growing body of evidence supporting the profile of PRX012, which is designed to target all aggregated forms of Abeta with high binding potency. The data further support the ongoing clinical development of PRX012 as a potential best-in-class treatment for Alzheimer’s disease that could enable improved access and more convenient administration for patients and caregivers.