Nonclinical Safety Assessment of Antibody-Oligo Conjugates from IND-enabling through Late-Stage Clinical Trials (S08-4)

Antibody oligonucleotide conjugates (AOCs) combine the tissue specificity of monoclonal antibodies with the precision and potency of oligonucleotides to enable the targeted delivery of oligonucleotides to previously untreatable tissues and cell types. AOC 1001 is comprised of a siRNA conjugated to an antibody targeting human transferrin receptor 1 (TfR1), designed for functional delivery to muscle cells, where it can reduce the levels of myotonic dystrophy protein kinase (DMPK) mRNA implicated in myotonic dystrophy type 1 (DM1) pathogenesis. DM1 is a rare dominantly inherited progressive neuromuscular disease caused by toxic gain-of-function mutation in the DMPK gene. The nonclinical safety strategy and regulatory feedback of AOC 1001 supporting IND through late-stage clinical trials will be discussed.