Prothena Corporation plc shared data on three investigational product programs for the treatment and prevention of Alzheimer's disease, PRX005, PRX012 and PRX123, at the Alzheimer's Association International Conference®? 2023 (AAIC®?) being held July 16-20, 2023 in Amsterdam, Netherlands and virtually. PRX005 Phase 1 Clinical Trial, Single Ascending Dose (SAD) Portion: Prothena: PRX005, A Novel Anti-MTBR Tau Humanized Monoclonal Antibody: Results from the Single Ascending Dose Portion of a First-in-Human Double-Blind, Placebo-Controlled, Phase 1 Clinical Trial: The results of the Phase 1 clinical trial SAD portion showed that all three dose level cohorts (low, medium, high) of PRX005 were considered generally safe and well tolerated, meeting the Phase 1 clinical trial S AD portion primary objective and supporting evaluation of doses in the MAD portion of the ongoing Phase 1 clinical trial.

PRX005 also met key pharmacokinetic (PK) and immunogenicity secondary endpoints. Plasma drug concentrations of PRX005 increased in a dose-proportional manner. As planned, cerebral spinal fluid (CSF) drug levels were measured in the high dose cohort and reached sufficient CSF concentrations to predict pharmacological targeting of MTBR tau in the central nervous system (CNS) (day 29 CSF:plasma ratio=0.2%).

On July 10, 2023, Prothena announced that Bristol Myers Squibb exercised its $55 million option under the global neuroscience research and development collaboration to obtain the exclusive worldwide commercial rights for PRX005. PRX123, a potential first-in-class investigational dual Ab/tau vaccine designed for the treatment and prevention of disease, is a dual-target vaccine targeting key epitopes within the N-terminus of Ab and MTBR-tau to simultaneously promote amyloid clearance and blockade of pathogenic tau. PRX012, an investigational next-generation anti-Ab antibody, was designed as a subcutaneous IgG1 mAb to target aggregated forms of Ab, including protofibrils and plaques, with high binding affinity.

PRX012 is currently being investigated in a Phase 1 clinical trial for the treatment of Alzheimer’s disease. Preclinical data have demonstrated binding of PRX012 to beta amyloid plaques and oligomers with high affinity, allowing effective Aß plaque occupancy and removal at relatively lower dose ranges, optimal for subcutaneous delivery. Preclinical data have also demonstrated clearance of both pyroglutamate modified and unmodified Aß plaque in brain tissue at concentrations of PRX012 estimated to be clinically achievable in the central nervous system with subcutaneous delivery.