Aligos Therapeutics Reports Positive Phase 2a Results for ALG-055009 in MASH Treatment

Aligos Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced encouraging results from its Phase 2a HERALD study of ALG-055009, a thyroid hormone receptor beta (THR-β) agonist, in subjects with metabolic-dysfunction associated steatohepatitis (MASH). The randomized, double-blind, placebo-controlled trial enrolled 102 subjects with presumed MASH and stage 1-3 liver fibrosis. Participants were assigned to receive either one of four doses (0.3, 0.5, 0.7, or 0.9 mg) of ALG-055009 or a placebo for 12 weeks.

Key endpoints of the study included safety, tolerability, pharmacokinetics, and changes in liver fat content measured by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF), along with other non-invasive biomarkers and tests. The 12-week study revealed that doses of 0.5 mg to 0.9 mg of ALG-055009 led to statistically significant reductions in liver fat, with placebo-adjusted median relative reductions of up to 46.2%. Additionally, up to 70% of subjects achieved a ≥30% relative reduction in liver fat compared to baseline.

Throughout the study, ALG-055009 was well-tolerated, with no serious adverse events reported. Most treatment-emergent adverse events were mild to moderate, with only one discontinuation due to worsening insomnia in a subject with pre-existing insomnia. Importantly, the incidence of gastrointestinal-related adverse events was similar between the ALG-055009 and placebo groups, with a lower incidence of diarrhea in the ALG-055009 groups.

The treatment with ALG-055009 also resulted in significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B, along with dose-dependent increases in sex hormone-binding globulin (SHBG), a marker of THR-β target engagement in the liver.

Rohit Loomba, MD, MHSc, Chief of the Division of Gastroenterology and Hepatology at the University of California, San Diego, remarked on the data’s significance, emphasizing the potential of ALG-055009 not only for the improvement in resolving MASH but also for fibrosis improvement and cardiovascular risk reduction if the non-invasive test data are confirmed in future trials.

Lawrence Blatt, Ph.D., MBA, Chairman, President, and CEO of Aligos Therapeutics, highlighted the design goals for ALG-055009, which aimed to create a best-in-class THR-β agonist with enhanced potency and a superior pharmacokinetic profile. The trial data suggests that these objectives have translated into robust improvements in liver fat reduction and a favorable tolerability profile, which is crucial for long-term MASH treatment adherence. Blatt emphasized the potential of ALG-055009 to support better patient adherence to MASH treatment regimens.

The company is currently in discussions with potential partners to fund the continued development of ALG-055009 and plans to complete activities required for a Phase 2b study by mid-2025. Further results and analyses from the study are expected to be presented at an upcoming scientific meeting.

On the broader issue of MASH, this liver condition is a consequence of poor diet and insufficient exercise, leading to fatty deposits in the liver. It affects a significant portion of the global population and can progress to serious liver damage, including cirrhosis, if not addressed. A newly approved THR-β agonist marks a significant development in treating this growing patient population. The HERALD study’s promising results underscore the importance of continued research and development in this field to improve patient outcomes.