Alnylam achieves delivery of novel siRNAs conjugates to the central nervous system

May 8 2018

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the Company has achieved delivery of novel small interfering RNA (siRNA) conjugates to the central nervous system (CNS) and is planning to advance a pipeline of investigational RNAi therapeutics into clinical development. RNAi therapeutics have the potential to prevent or reverse neurodegenerative diseases caused by dominantly inherited genes, such as in Alzheimer's, Huntington's, Parkinson's, and amyotrophic lateral sclerosis (ALS), where there are limited to no treatment options. The Company plans to complete selection of its first CNS-targeted development candidate (DC) in 2018, and then expects to file its first investigational new drug (IND) or IND equivalent in late 2019/early 2020, with the potential for one or more INDs per year thereafter. Alnylam's planned emerging pipeline of CNS-directed investigational RNAi therapeutics is in addition to the Company's continued advancement of GalNAc-conjugated siRNAs toward a broad range of liver-expressed disease targets for the Company's Genetic Medicine, Cardiometabolic Disease, and Hepatic Infectious Disease Strategic Therapeutic Areas (STArs).

"Over the past 15 years, Alnylam has advanced conjugate-based delivery of investigational RNAi therapeutics with multiple transformative discoveries, paving the way for development of a whole new class of innovative medicines. We have now applied our learnings, including additional chemistry advances, to enable delivery of siRNAs beyond the liver to the CNS, where there are a large number of unmet needs well suited for RNAi therapeutics. As we begin to advance our CNS pipeline, initial efforts are focused on genetically validated CNS targets, use of biomarkers for initial proof-of-concept, and disease settings with high unmet need and a definable path to regulatory approval and patient access," said Kevin Fitzgerald, Ph.D., Senior Vice President, Research at Alnylam. "We believe the robust potency, durability, and tolerability of liver-targeted RNAi therapeutics in Alnylam's broader clinical pipeline set a strong foundation for the future development of investigational CNS-targeted RNAi therapeutics, where we expect to select our first development candidate later this year."

Alnylam presented initial results from preclinical studies at the TIDES: Oligonucleotide and Peptide Therapeutics 2018 Annual Meeting being held May 7-10 in Boston, MA., as part of a plenary talk entitled "Delivering on RNAi Therapeutics: Patisiran and Beyond." In a rat preclinical study, a single intrathecal injection of a novel siRNA conjugate resulted in broad distribution across the brain and spinal cord regions. Robust and highly durable silencing of a disease target gene transcript was seen in all key anatomical regions of the brain and spinal cord. Specificity of the silencing effect was confirmed with a second siRNA conjugate targeting an independent gene transcript ubiquitously expressed in the CNS. The novel siRNA conjugates utilize Alnylam's enhanced stabilization chemistry (ESC) platform with further modifications to enable broad CNS delivery and efficient uptake in neuronal cells.