1. INHBE siRNA therapeutics for obesity treatment

INHBE siRNA drugs enable liver-targeted delivery, silencing INHBE in hepatocytes to reduce Activin E production. This restores lipolysis, enhances lipid mobilization, and reduces abdominal fat.
Unlike GLP-1, which causes one-third muscle loss, INHBE siRNA preserves lean mass by targeting adipose metabolism.With bi-annual dosing, it surpasses the weekly/biweekly injections of GLP-1, offering a superior option for sustainable weight management.
Given INHBE's involvement in glucose metabolism, combining INHBE siRNA drugs with GLP-1 agents shows synergistic effects for glycemic control and weight reduction.

2. Highlights and differentiations

Compared to Alnylam’s GalNac L96, the internally self-developed GalNac L851 has excellent liver-targeted delivery capabilities;
In AAV-hINHBE mouse and cyno monkeys, a single subcutaneous dose of asset results in significant, dose-dependent suppression of hepatic INHBE expression, showing non-inferior efficacy compared to ALN-INHBE (Alnylam);
A reduced off-target profile compared to ALN-INHBE.

3. Data and results

In Hep3B cell line, asset demonstrates significant downregulation of INHBE mRNA expression, as validated by qRT-PCR.
Compared with Alnylam’s Ref, asset has a reduced off-target profile, as validated by RNAseq

Asset induced significant suppression of INHBE expression in liver tissues ofAAV-hINHBE mice, as validated by qRT-PCR ;
Asset elicited dose-responsive suppression of hepatic INHBE expression in cyno monkeys, as validated by qRT-PCR .