Aligos Therapeutics (ALGS) Study Result summary

Study design and methodology

• 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 dose groups (0.3–0.9 mg) and placebo for 12 weeks.

• Only subjects over 85 kg were enrolled in the 0.9 mg group to address body weight variability.

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

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

• Study enrolled rapidly over six weeks, reflecting high interest in MASH therapies.

Efficacy and biomarker results

• Statistically significant, dose-dependent reductions in liver fat by MRI-PDFF at week 12 in 0.5, 0.7, and 0.9 mg groups, with up to 46.2% placebo-adjusted median reduction at 0.7 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-related increase in SHBG were observed.

• ALG-055009 showed greater liver fat reduction compared to published data for resmetirom, though no head-to-head trials were conducted.

• The 0.7 mg and 0.9 mg doses showed the greatest efficacy, with p-values <0.001 versus placebo.

Safety and tolerability

• ALG-055009 was well tolerated, with no serious adverse events or clinical evidence of hyper- or hypothyroidism.

• Most treatment-emergent adverse events were mild or moderate; one discontinuation occurred due to insomnia.

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

• Incidence of gastrointestinal events, including diarrhea, was similar or lower than placebo and lower than the approved comparator.

• Favorable tolerability profile supports potential for long-term use in MASH treatment.