Prothena Presents New Research in the Treatment of Alzheimer’s Disease at Alzheimer’s Association International Conference 2023 (AAIC) - Seite 2

PRX123 Preclinical Study Results

Poster #82687: Immunological response to dual Aβ/Tau vaccine PRX123 surrogate and effects on brain amyloid plaques in rapidly depositing transgenic animal model

Preclinical results demonstrated that a PRX123 vaccine surrogate elicited robust antibody responses that bound with high avidity to Aβ plaques in Alzheimer’s disease brain ex vivo and significantly reduced Aβ brain plaques in a transgenic mouse model of Alzheimer’s disease pathology. The results support the continued development of PRX123, a dual Aβ-tau conjugated linear peptide vaccine designed to treat and/or prevent Alzheimer’s disease, and represent the first time that a dual target vaccine for Alzheimer’s disease has been shown to reduce pathology in a transgenic animal model.

PRX012 Preclinical Study Results (encore presentation)

Poster #74811: Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of Toxic Aβ Protofibrils and Robust Clearance of Pyroglutamate-Modified Aβ

Results from two preclinical studies were presented comparing a PRX012-surrogate^* (PRX012s) to lecanemab and donanemab^†. In the first study, Surface Plasmon Resonance (SPR) was used to compare PRX012s to lecanemab and showed that PRX012s had approximately 20-fold higher affinity to Aβ protofibrils when compared to lecanemab, tested under the same conditions. In the second study, ex vivo using post-mortem Alzheimer’s disease brain tissue, PRX012s demonstrated to robustly clear pyroglutamate-modified Aβ deposited in plaques more potently than donanemab.

About PRX005

PRX005 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity to the R1, R2, and R3 repeats within the MTBR of tau and targets both 3R and 4R tau isoforms. MTBR tau has been shown in preclinical studies to be involved in the pathological spread of tau. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer’s disease. Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with Alzheimer’s disease. Recent publications suggest that during the course of Alzheimer’s disease progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau “seeds” containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages and tau tangles in Alzheimer’s disease to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in Alzheimer’s disease animal models. In these preclinical models, PRX005 demonstrated significant reduction of intraneuronal tau pathology and protection against behavioral deficit in a tau transgenic mouse model and complete blockade of neuronal tau internalization in vitro.