追踪80亿美元的阿尔茨海默病诊断市场

Introduction.......................................................................................................................3Background on Alzheimer’s Disease.................................................................................3Amyloid-Beta PET Agents................................................................................................14 We believe the radiopharmaceutical industry represents one of the most compelling seculargrowth opportunities in biotech in the next three to five years. Defying the conventional belief thatit remains a niche market, we are optimistic that the recent resurgence in investor and big pharmainterest that culminated in four high-profile acquisitions (Point Biopharma by Eli Lilly, RayzeBioby Bristol Myers, Fusion Pharma by AstraZeneca, and Mariana Oncology by Novartis), coupledwith Novartis’s recent increase in Pluvicto peak sales guidance (to $5 billion, from $3 billion pre- It is our aim to provide a yearly update on radiopharmaceuticals to serve as a resource for inves-tors who would like to gain knowledge and understanding in this rapidly evolving space that has attracted a significant inflow of investment. Our first edition (see:Bioluminescence—Illuminatingthe Road Less Traveled in Biotech: Radiopharmaceuticals) provided an in-depth analysis of the fieldat large, and we refer readers to that report for a historical background on the field and fundamentalnuclear chemistry concepts. In our second edition (see:Illuminating the Road Less Traveled in Bio-tech: Radiopharmaceuticals – Second Edition), we focused on elucidating the supply chain portion of the industry, given that we view this as one of the more obscure and difficult-to-understand and -visualize areas. We also provided an in-depth overview of the various medically relevant radio-isotopes that are being explored for therapeutic applications, a description of current and futuretrends, and a comprehensive list of radiopharmaceutical companies in both the therapeutic and In the current edition, we take a departure from the therapeutic landscape and focus instead on therole of diagnostics. Given that the PET imaging market is a promising area of growth for radiophar-maceuticals, in our view, we aim to elucidate the evolving role of PET in the context of diagnosingAlzheimer’s disease. We believe this application represents a material use-case for radiopharma-ceuticals beyond oncology and provides an example of the diagnostic power of medically relevant Alzheimer’s disease is the most common form of dementia, accounting for 60%-70% of all de-mentia cases. According to theAlzheimer’s Association, more than 7 million Americans are livingwith Alzheimer’s disease; the majority (74%) are 75 years of age or older. It is estimated thatroughly 11% of adults 65 years or older have Alzheimer’s disease, and women constitute roughlytwo-thirds of all Alzheimer’s disease occurrences. Cases continue to climb, and by 2050, nearly13 million Americans could be living with Alzheimer’s disease (though this estimate could be re- Beyond age and gender, genetics (APOEin particular) is an important risk factor for Alzheimer’s. WhileAPOE ε2(occurring in 5%-10% of the population) potentially provides protection againstthe disease,APOE ε4(present in 15%-25%, though only 2%-5% have two copies) appears to in-crease the risk of developing Alzheimer’s disease, especially when two copies are present. SinceAPOE ε4is also a risk factor for developing amyloid-related imaging abnormalities (ARIA; a sideeffect of anti-amyloid therapies), the label for Leqembi suggests thatAPOE ε4testing be carriedout before initiating treatment to help determine a patient’s risk for developing ARIA. Given these Alzheimer’s Disease Pathology Cognitive decline associated with Alzheimer’s disease results from two classes of abnormal struc-tures in the brain: amyloid plaques and neurofibrillary tangles (also known as NFTs). These struc-tures are densely packed filaments of amyloid-beta peptides and tau proteins, respectively (exhibit1). They accumulate in the brain and are correlated with cell death, tissue loss, and consequentialcognitive decline. Amyloid plaques form between neurons when amyloid-beta peptides (which NFTs contribute to cognitive decline in a different manner. In healthy individuals, tau proteins helpform microtubules that transport nutrients within nerves in the brain. However, in patients withAlzheimer’s disease, these microtubules break down, and the “free” tau proteins stick together due paired helical filaments, or PHFs. These filaments are the building blocks of NFTs. Without func-tional microtubules, the neurons are starved of nutrients, which can lead to nerve death throughloss of axonal transport and blockage of nuclear transport. NFTs accumulate over the course ofthe disease and trigger cognitive decline. Unlike amyloid plaques, which can begin accumulatingdecades before cognitive symptoms are evident, NFTs becom