Principle Toxicologist Denali Therapeutics South San Francisco, California, United States
This presentation was created by Dr. Katie Sokolowski. It will be presented by her colleague, Dr. René Meisner.
This talk will describe the development of a human transferrin receptor (TfR)-binding molecule to transport ASO (oligonucleotide transport vehicle [OTV]) across the BBB in mice and non-human primates and points to consider when developing the nonclinical safety strategy. Systemically delivered OTV drives significant, cumulative, and sustained knockdown of the ASO target across multiple CNS regions and all major cell types. Systemic OTV delivery enables more uniform ASO biodistribution and knockdown compared to two other clinically relevant ASO delivery routes. Together, the data support systemically delivered OTV as a potential therapeutic platform for neurological disorders. However, molecules with two targets require special consideration when designing the nonclinical safety strategy. This talk will also cover points to consider to address safety concerns around these unique molecules with two targets.
