Prothena Preclinical Data Backs Next-Generation Anti-Amyloid Beta Antibody

 

• Data from oral presentation adds to growing body of evidence supporting the profile of PRX012, which is designed to target all aggregated forms of amyloid beta with high binding potency
• Demonstrated 20-fold higher affinity to amyloid beta soluble protofibrils when compared to lecanemab
• Clears pyroglutamate-modified amyloid beta at lower concentrations when compared to donanemab

 

Prothena Corporation plc  (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today announced new preclinical data from its PRX012 program, a potential best-in-class anti-amyloid beta (Aβ) 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 (AD/PD) in Gothenburg, Sweden.

To build a more in-depth understanding of the profile of PRX012 and its potential as a best-in-class anti-Aβ treatment for Alzheimer’s disease, two preclinical studies presented in an oral presentation at AD/PD 2023 compare a PRX012-surrogate^* (PRX012s) to approved and investigational molecules. Surface Plasmon Resonance (SPR) was used to compare PRX012s to lecanemab⁺ and showed that PRX012s had approximately 20-fold higher affinity to Aβ 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 Aβ deposited in plaques. Study results showed that lower concentrations of PRX012s induced more potent and robust clearance of pyroglutamate-modified Aβ as compared to donanemab⁺. In the experiment, microglia simultaneously phagocytosed non-pyroglutamate-modified Aβ and pyroglutamate-modified Aβ in the presence of PRX012s, indicating that high opsonization efficiency of plaques by PRX012s was sufficient to clear both forms of Aβ.

“These new preclinical data add to the scientific rationale of the PRX012 program, which has the potential to deliver a next-generation Alzheimer’s disease treatment and enable a more convenient administration for patients and caregivers,” said Wagner Zago, Ph.D., Chief Scientific Officer at Prothena. “With more than 55 million people worldwide estimated to be living with Alzheimer’s disease or other dementias, the timely delivery of improved disease modifying treatments is critical for these patients and their families. Prothena is committed to delivering a patient-centric, best-in-class Aβ-targeting antibody with the potential to robustly and safely deplete Aβ plaques.”

These data add to the growing body of evidence supporting the profile of PRX012, which is designed to target all aggregated forms of Aβ 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.

https://www.biospace.com/article/releases/prothena-presents-new-preclinical-data-supporting-best-in-class-profile-of-prx012-a-next-generation-anti-amyloid-beta-antibody-at-ad-pd-2023/