ALNYLAM PHARMACEUTICALS, INC.

Additional Pipeline Progress

•Advanced mivelsiran, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) for the treatment of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease.

◦Completed enrollment in the cAPPricorn-1 Phase 2 clinical trial in patients with CAA.

◦Initiated a Phase 2 clinical trial in patients with Down syndrome-associated Alzheimer's disease.

◦Shared additional Phase 1 data in early-onset Alzheimer's disease at the Alzheimer's Association International Conference (AAIC) 2026. An analysis of safety data from single- and multiple-doses of mivelsiran showed no evidence of increased risk of amyloid-related imaging abnormality (ARIA) events. Results also showed robust, durable reductions in CSF soluble amyloid beta precursor protein (sAPPβ) and amyloid beta 42 (Aβ42), with up to 30 months of treatment exposure. The most common adverse events (AEs) were procedural pain and procedural headache, and no serious or severe AEs were deemed related to study drug.

•Presented preclinical data and Phase 1 design details at AAIC 2026 for ALN-5288, an investigational RNAi therapeutic targeting microtubule-associated protein tau (MAPT) for Alzheimer's disease and tauopathies.