28 December 2021 - - US-based RNAi therapeutics company Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) has submitted a Clinical Trial Authorization application to The Medicines and Healthcare Products Regulatory Agency in the United Kingdom to initiate a Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein for the treatment of Alzheimer's disease and cerebral amyloid angiopathy, the company said.

The company plans to initiate the Phase 1 study in patients with early-onset AD in early 2022, upon obtaining MHRA approval, and expects to report initial human data at or around year-end 2022.

ALN-APP represents the first-ever RNAi therapeutic targeting CNS diseases. The clinical candidate was designed using Alnylam's proprietary C16 conjugate technology for the delivery of short interfering RNA (siRNA) to the CNS. As such, ALN-APP represents the start of Alnylam's expansion of RNAi therapeutic opportunities in extra-hepatic tissues.

ALN-APP is being advanced in partnership with Regeneron as part of the companies' 2019 agreement.

Alnylam will lead global development and commercialization of ALN-APP, and Regeneron has exercised its 50-50 co-development and co-commercialization option under the collaboration.

ALN-APP is an investigational, intrathecally administered RNAi therapeutic targeting amyloid precursor protein in development in collaboration with Regeneron Pharmaceuticals for the treatment of Alzheimer's disease and cerebral amyloid angiopathy.

Genetic mutations that increase production of APP or alter its cleavage cause early-onset AD, early-onset CAA, or both.

ALN-APP is designed to decrease APP mRNA in the central nervous system, to decrease synthesis of APP protein and all downstream intracellular and extracellular APP-derived cleavage products, including amyloid beta.

Reducing APP protein production is expected to reduce the secretion of Aβ peptides that aggregate into extracellular amyloid deposits and reduce the intraneuronal APP cleavage products that trigger the formation of neurofibrillary tangles and cause neuronal dysfunction in Alzheimer's disease.

ALN-APP is the first program utilizing Alnylam's C16 conjugate technology, which enables enhanced delivery to cells in the CNS. The safety and efficacy of ALN-APP have not been evaluated by the FDA, EMA, or any other health authority.

Alzheimer's disease is the most common neurodegenerative disease and the most common form of dementia, affecting over 30m people worldwide.

AD is characterized by progressive memory loss and cognitive decline, with neuropathological accumulation of amyloid plaques, neurofibrillary tangles, and neuroinflammation, ultimately resulting in significant brain atrophy.

Disease progression results in progressive loss of independence, increased caregiver burden, institutionalization, and premature death.

Early-onset Alzheimer's disease refers to a subgroup of AD with symptom onset prior to the age of 65, representing approximately 4% to 6% of all AD.

EOAD is the leading cause of dementia in younger individuals and is a significant cause of disability and early mortality.

Available treatment options include symptomatic treatment and treatment to reduce amyloid deposits in the brain. There are currently no available treatments that have been shown to halt or reverse the progression of the disease.