On the 3rd, AprilBio Co.,Ltd. released early preclinical pharmacodynamic (PD) data for its dual-target RNAi candidate “APB-O-001.” APB-O-001 is a bispecific siRNA complex for the treatment of dyslipidemia.
The company announced that it successfully suppressed the expression of both PCSK9 and APOC3 genes simultaneously with a single administration. This is seen as a positive sign for entering the RNA therapeutics market and securing a new pipeline.
In a GalNAc-conjugated siRNA liver-targeted study conducted by AprilBio Co.,Ltd., APB-O-001 simultaneously suppressed PCSK9 and APOC3 mRNA in liver tissue following a single administration to mice. The experiment also included inclisiran and flozaciran—representative single-target RNA therapeutics targeting each respective target—as control groups.
In the highest-dose group, PCSK9 mRNA levels decreased to as low as approximately 23% of the control group (approximately 77% inhibition), while APOC3 mRNA levels decreased to as low as approximately 26% of the control group (approximately 74% inhibition). Notably, on day 7 post-administration, simultaneous inhibition of both targets by more than 70% was observed in the same animals. The negative control group (si-scramble) maintained baseline levels throughout the entire study period.
AprilBio Co.,Ltd. stated, “These data demonstrate that although APB-O-001 is a dual-target RNAi designed to attack two targets simultaneously, its ability to inhibit each target individually remains uncompromised,” adding, “The fact that we achieved results comparable to or better than those of a single-target compound validated in an equidose comparison within the same experiment provides a crucial basis for subsequent development.”
The representative added, “Since Arrowhead’s primate data supports the clinical feasibility of the dual-target approach, we plan to rapidly expand the development phase to include durability assessments and large-animal studies.”
