Biogen Inc. and Ionis Pharmaceuticals, Inc. announced that topline data from a Phase 1b placebo-controlled, multiple ascending dose clinical study showed that BIIB080/IONIS-MAPTRx met its primary objective of safety and tolerability in patients with mild Alzheimer's disease. The study demonstrated robust time and dose dependent lowering of tau protein in cerebrospinal fluid (CSF) over the three-month treatment period and sustained reductions during the six-month post-treatment period. In patients receiving BIIB080, there were dose-dependent decreases in the concentration of total-tau in CSF eight weeks post-last dose (Day 141) with a mean percentage reduction of 30 percent, 40 percent and 49 percent in the low, medium and high dose groups treated every four-weeks, respectively, and 42 percent in the group treated every 12 weeks. Total-tau in the CSF continued to decline 16 weeks post-last dose in patients treated with BIIB080 in the high dose four-week and 12-week dose groups, showing a 55 percent and 49 percent mean reduction from baseline, respectively. CSF was not collected 16 weeks post-last dose in the low and medium four-week dose groups. There were similar dose-dependent decreases in the levels of phosphorylated tau. All participants (n=46) completed the Multiple Ascending Dose (MAD) period and 43 participants completed the Post-Treatment (PT) period (3 participants voluntarily withdrew). These data were presented in a poster session at the 2021 Alzheimer's Association International Conference (AAIC) held virtually and in Denver, Colo., July 26 30. Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive and functional decline resulting in significant disability. Until recently, treatment was limited to management of symptoms. BIIB080 is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) mRNA and prevent production of tau protein. Growing evidence suggests that aggregated, hype phosphorylated tau may be a key driver of neurodegeneration in Alzheimer's disease as well as other tauopathies including progressive supranuclear palsy and frontotemporal degeneration. In preclinical studies in MAPT transgenic mice, MAPT-targeted antisense treatment demonstrated robust tau-lowering in CNS tissues and prevention and reversal of disease. The primary objective of the Phase 1b first-in-human study was to assess safety and tolerability of multiple intrathecal (IT) bolus administrations of BIIB080. The study was divided into two parts: Part 1, a MAD study of 46 patients with mild Alzheimer's disease comprising a three-month Treatment Evaluation Period and a six-month PT period; Part 2, an open label long-term extension study comprising a 12-month Treatment Evaluation Period and a four- or six-month PT period. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to IT bolus administrations of BIIB080 or placebo. Patients aged 50-74 years with mild Alzheimer's disease and confirmed amyloid positivity (via CSF) at screening were considered eligible. Part 1 is now complete; Part 2 is currently ongoing (EudraCT: 2016-002713-22; NCT03186989). The characteristics of patients at baseline were representative of relatively younger, mild Alzheimer's disease patients and were generally similar across trial groups. All adverse events were mild to moderate in severity with no serious adverse events occurring in any patients that received BIIB080. There were no deaths, dose-limiting adverse events or dosing discontinuations.