ALG-055009 was designed by Aligos to be a potent best-in-class oral, small molecule thyroid receptor beta agonist (THR-β) for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

1.66 billion people worldwide are living with MASH and its precursor metabolic dysfunction associated steatotic liver disease (MASLD), making it the most common chronic liver disease worldwide. It is a leading cause of liver-related morbidity, including cirrhosis, hepatocellular carcinoma, liver transplant, and end-stage liver disease.¹

ALG-055009 was designed to improve upon the potency and selectivity of competitor THR-β agonists and was further optimized for pharmacokinetics (PK). Activating THR-β is associated with systemic lipid lowering, increased bile acid synthesis, improvement in the conversion of T4 to T3, and fat oxidation, leading to reversal of steatosis.²

Phase 1 studies have demonstrated after single and multiple daily doses that ALG-055009 was well tolerated, had dose proportional PK and low variability, and demonstrated expected thyromimetic effects.

The Phase 2a HERALD study was designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral daily doses of ALG-055009 for 12 weeks. Topline HERALD data were presented in September 2024, demonstrating that ALG-055009 dose groups met the primary endpoint with statistically significant reductions in liver fat at Week 12 as measured by MRI-PDFF.

ALG-000184 was derived from initial IP licensed from the laboratory of Dr. Raymond Schinazi at Emory University, which was further optimized by Aligos. Our potent best/first-in-class oral small molecule capsid assembly modulator (CAM-E) is being developed for chronic hepatitis B (CHB).

CHB is the most common chronic viral infection in the world. There are more than 296 million chronic carriers worldwide and approximately 1.5 million individuals become newly infected every year. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.³

ALG-000184 is designed to exploit the dual role of CAMs by preventing the establishment and replenishment of cccDNA levels and its derived transcripts by reducing expression of viral markers such as DNA, RNA, and the relevant antigens (HBsAg, HBeAg, HBcrAg).

Phase 1a studies have demonstrated after single and multiple daily doses that ALG-000184 was well-tolerated, with no safety signals observed, and demonstrated linear PK and excellent antiviral activity.

In longer term Phase 1b studies of ALG-000184 300mg QD x ≤96 weeks ± Entecavir (ETV), ALG-000184 monotherapy has demonstrated best-in-class reductions in HBV DNA, RNA, HBsAg, HBeAg, and HBcrAg. Dosing is ongoing through 2025 with interim data readouts expected at upcoming scientific conferences.

Phase 2 enabling activities are underway, with a planned submission of Phase 2 protocol to the FDA and globally in Q1 2025. Aligos has received FDA, CHMP (EMA), and National Medical Products Administration in China feedback supporting subsequent studies utilizing the chronic suppressive therapy pathway.

Xiamen Amoytop Biotech Co., Ltd. will sponsor and perform a Phase 1b exploratory clinical study evaluating the efficacy and safety of ALG-000184 in combination with PEGBING® (Mipeginterferon alfa-2b) in chronic hepatitis B (CHB) patients in China.

PEGBING®, independently developed by Amoytop, is the world's first 40kD pegylated interferon α-2b injection. With dual effects of inhibiting viral replication and enhancing immunity, PEGBING® is mainly used in the clinical treatment of viral hepatitis and is the first-line drug for the antiviral treatment of CHB, which plays an important role in improving the clinical cure rate of hepatitis B and reducing the risk of liver cancer.

The Phase 1b study will be a randomized, double blinded, active controlled study to evaluate the safety, pharmacokinetics, and antiviral activity of oral once daily doses of 300 mg ALG-000184 + PEGBING® + entecavir (ETV) compared with either once daily 300 mg ALG-000184 + ETV or PEGBING® + ETV in treatment naïve or currently-not-treated HBeAg-positive and nucleos(t)ide analog (NA) suppressed HBeAg-negative subjects with CHB for 48 weeks. The clinical study is expected to begin after approval by the National Medical Products Administration in China.

ALG-097558 was built as a potent ritonavir-free pan-coronavirus protease inhibitor (PI) in collaboration with Katholieke Universiteit Leuven (KU Leuven), the Center for Innovation and Stimulation of Drug Discovery (CISTIM) and the Centre for Drug Design and Discovery (CD3).

In preclinical studies, ALG‑097558 has been shown to be at least 6-fold more potent than nirmatrelvir and other PIs in clinical development against a panel of SARS-CoV-2 variants. It has demonstrated broad pan-coronavirus activity, including against SARS and MERS.

In Phase 1 clinical studies, single doses and multiple doses have been well tolerated with an acceptable PK profile that indicates ritonavir boosting is not required.

Specific clinical and nonclinical studies for the ALG-097558 program are being funded with federal funds from the NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93023C00052. We expect to receive approximately $12.3 million in funds across these two NIH awards and contracts to support these activities.

ALG-097558 is expected to begin three clinical trials

• AGILE University of Liverpool, a UK government supported platform trial (MRC and Wellcome Trust funding), will sponsor and perform a study in high-risk COVID patients evaluating ALG-097558 as monotherapy or in combination with remdesivir
• The NIAID will sponsor clinical studies to evaluate pharmacokinetic (PK) differences in special populations (renal/hepatic impairment subjects)