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 virus infection.

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 1 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 1 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.

The Phase 2 B-SUPREME study (NCT06963710) is a randomized, double-blind, active-controlled multicenter study evaluating the safety and efficacy of ALG-000184 monotherapy compared with tenofovir disoproxil fumarate in approximately 200 untreated HBeAg+ and HBeAg- adult subjects with chronic HBV infection for 48 weeks. The primary endpoint in the HBeAg+ part will be HBV DNA < LLOQ (10 IU/mL, target detected [TD] or target not detected [TND]) and the primary endpoint in the HBeAg- part will be HBV DNA < LLOQ (10 IU/mL, target not detected [TND]). The study will also evaluate the safety, pharmacokinetics, and other secondary and exploratory biomarkers, including reductions in HBV antigens and other markers of HBV infection. Dosing began in August 2025, with interim data projected in 2026 and topline data anticipated in 2027.

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-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 $13.8 million in funds across these two NIH awards and contracts to support these activities.

ALG-097558 began three clinical trials in 2024

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

Aligos has developed an ASO platform utilizing novel monomers that could potentially reduce ASO toxicity and improve ASO liver to kidney ratio. After rigorous screening, 10 HBV ASOs emerged as lead candidates, which have shown favorable in vitro and in vivo profiles when compared with other candidates currently in clinical studies.