Alnylam Pharmaceuticals Inc (ALNY)

[FooBarAndGrill]

ESC+ GalNAc conjugates utilize advanced design features to further improve specificity, including a glycol nucleic acid (GNA) modification in the antisense seed region of the siRNA, while maintaining potency and durability. The data presented at OTS indicated that incorporation of GNA destabilizes seed-driven pairing with partially complementary transcripts, thus greatly reducing potential off-target effects while maintaining on-target pairing and activity. Additionally, it was shown that GNA modifications confer enhanced specificity and a greater-than 6-fold improvement in therapeutic index as observed in pre-clinical studies in rodents. The ESC+ design is now being applied to all of Alnylam’s pre-clinical programs and has shown successful translation of potency from rodents to non-human primates. Alnylam intends to employ its ESC+ siRNA-conjugate platform in all future development programs.