Alzheimer’s Disease

Alzheimer’s disease is a devastating form of dementia that causes memory, thinking and behavior problems.

At the earliest stages, Alzheimer’s disease commonly results in difficulty in remembering new information because the disease starts in the part of the brain associated with learning and memory.

Alzheimer’s disease is the 7th leading cause of death in the United States, with more than 6 million Americans living with Alzheimer’s disease, making it the most common neurodegenerative disorder. By comparison, the number of individuals in the United States alive today that have ever had lung cancer (the most common form of cancer) is approximately 541,000. There is an urgent need for therapies that slow the progression and ultimately prevent Alzheimer’s disease to address this global healthcare crisis.

It is believed two different proteins – Aβ (amyloid beta) and tau – are primary contributors to Alzheimer’s disease pathology. Misfolded Aβ builds up to form plaques between nerve cells in the brain. Tangles of twisted tau fibrils spread from cell-to-cell and cause build up inside cells. People with Alzheimer’s disease develop these pathological hallmarks of the disease in a predictable pattern as the disease progresses, starting in the centers of the brain responsible for memory and spreading out from there to other regions of the brain.

Our team leverages this foundational knowledge along with insights gained over the last 20 years of drug development in the Alzheimer’s disease space to develop new approaches to address this complex disease.

Recent data suggests that timely intervention with anti-Aβ therapy results in statistically significant and clinically meaningful slowing of disease progression. These therapies have the potential to fundamentally change how we treat Alzheimer’s disease. These first-generation therapies are likely to require further development to increase patient access and enhance the patient experience.

Prothena’s Alzheimer’s disease portfolio spans next generation antibody immunotherapy, small molecule and vaccine approaches, geared toward building upon first generation treatments to advance the treatment paradigm.

Prothena’s ongoing Phase 1 study of PRX012, a potential best-in-class, next-generation subcutaneously delivered anti-Aβ antibody, is being developed for the potential treatment of Alzheimer’s disease. PRX012 has been granted Fast Track designation by the FDA.

In collaboration with Bristol Myers Squibb, the Phase 1 single ascending dose (SAD) portion of the study in healthy volunteers demonstrated dose-proportional PRX005 concentrations in plasma with robust central nervous system (CNS) penetration of this potentially best-in-class investigational anti-MTBR-tau antibody. Single doses of PRX005 across three dose cohorts were generally safe and well tolerated, meeting the primary objective of the study. The Phase 1 multiple ascending dose (MAD) portion of the study is ongoing in healthy volunteers and patients with Alzheimer’s disease. In July 2023, Bristol Myers Squibb exercised its option under the global neuroscience research and development collaboration to obtain the exclusive worldwide commercial rights for BMS-986446/PRX005. The BMS-986446/PRX005 program is being conducted by our partner Bristol Myers Squibb.