Aligos Therapeutics (ALGS) Study Result summary

Study design and objectives

• Phase 2a/2b HERALD study was a randomized, double-blind, placebo-controlled trial in 102 adults with MASH and liver fibrosis stages F1-F3 at 32 US centers, with four oral dose groups (0.3–0.9 mg) and placebo for 12 weeks.

• Dosing for the highest group was stratified by body weight, with only subjects over 85 kg receiving 0.9 mg.

• Baseline characteristics were balanced across arms, including age, BMI, diabetes prevalence, and liver fat content.

• Primary endpoint was relative change in liver fat by MRI-PDFF at Week 12; secondary endpoints included safety, tolerability, pharmacokinetics, and biomarker changes.

• Key opinion leaders contributed to study design and oversight.

Efficacy and biomarker results

• Doses of 0.5–0.9 mg achieved statistically significant, placebo-adjusted median liver fat reductions up to 46.2% at Week 12, with p-values <0.001 for 0.7 and 0.9 mg.

• Up to 70% of subjects in higher dose groups achieved ≥30% relative reduction in liver fat, predictive of histologic improvement.

• Significant reductions in atherogenic lipids (LDL-C, lipoprotein(a), apolipoprotein B) and dose-dependent increases in SHBG were observed.

• ALG-055009 showed greater liver fat reduction than resmetirom, the only approved THR-β agonist, though no head-to-head trials were conducted.

Safety and tolerability

• ALG-055009 was well tolerated, with no serious adverse events, no clinical evidence of hyper- or hypothyroidism, and only one discontinuation due to insomnia.

• Most adverse events were mild or moderate; 98% of treatment-emergent events were not severe.

• No clinically meaningful lab, ECG, or vital sign abnormalities were observed.

• Incidence of gastrointestinal events, including diarrhea, was similar or lower than placebo.

• Favorable tolerability profile supports potential for long-term treatment adherence.