Aligos Therapeutics, Inc.

Previous wording

We are a clinical-stage biotechnology company focused on developing novel therapeutics to address unmet medical needs in liver diseases and viral infections, including in the areas of chronic hepatitis B virus (HBV) infection, metabolic dysfunction-associated steatohepatitis (MASH), and coronavirus infections (e.g., SARS‑CoV‑2, SARS‑CoV, MERS‑CoV, and other related infections). The Aligos team has a demonstrated track record of success in early drug development and medicinal chemistry in liver and viral diseases, resulting in three potential best‑in‑class drug candidates currently in development.

Current wording

We are a clinical-stage biotechnology company focused on developing novel therapeutics to address unmet medical needs in liver diseases and viral infections, including in the areas of chronic hepatitis B virus (HBV) infection, metabolic dysfunction-associated steatohepatitis (MASH), and coronavirus infections (e.g., SARS‑CoV‑2, SARS‑CoV, MERS‑CoV, and other related infections) as well as obesity. The Aligos team has a demonstrated track record of success in early drug development and medicinal chemistry in liver and viral diseases, resulting in three potential best‑in‑class drug candidates currently in clinical development.

Previous wording

Our pipeline of drug candidates includes ALG‑000184 for chronic HBV infection, ALG‑055009 for MASH, ALG‑097558 for coronavirus infections, and a portfolio of preclinical programs. ALG‑000184 is our potential best‑/first‑in‑class Capsid Assembly Modulator (CAM‑E) for chronic HBV infection with enhanced pharmacologic properties vs. competitor CAM‑E drugs and has demonstrated greater HBV DNA suppression compared to the standard of care, nucleos(t)ide analogs (NAs), as well as multi-log 10 reductions in viral antigens in Phase 1 clinical studies conducted to date. ALG‑055009 is our potential best‑in‑class thyroid hormone receptor beta (THR‑β) agonist for MASH with pharmacologic properties that appear to be enhanced based on data to date vs. competitor THR-β agonists. Phase 2a topline data demonstrated 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 is our potential best‑in‑class small molecule pan-coronavirus 3CL protease inhibitor (PI), which has been at least 3-fold more potent in cell-based assays of coronavirus infection than other approved CoV PIs and we believe can be dosed twice daily without the requirement for ritonavir co-dosing based on Phase 1 clinical studies conducted to date.

Current wording

Our pipeline of drug candidates includes pevifoscorvir sodium (previously known as ALG‑000184) for chronic HBV infection, ALG‑055009 for obesity and MASH, ALG‑097558 for coronavirus infections, and a portfolio of preclinical programs. Pevifoscorvir sodium is our potential best‑/first‑in‑class Capsid Assembly Modulator (CAM‑E) for chronic HBV infection which has shown in pre-clinical testing to have enhanced pharmacologic properties vs. competitor CAM‑E drugs and greater HBV DNA suppression compared to the standard of care, nucleos(t)ide analogs (NAs), and has shown multi-log 10 reductions in viral antigens in Phase 1 clinical studies conducted to date. ALG‑055009 is our potential best‑in‑class thyroid hormone receptor beta (THR‑β) agonist for obesity and MASH with pharmacologic properties that appear to be enhanced based on data to date vs. competitor THR-β agonists. Phase 2a topline data in MASH demonstrated 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 is our potential best‑in‑class small molecule pan-coronavirus 3CL protease inhibitor (PI), which has been at least 3-fold more potent in cell-based assays of coronavirus infection than other approved CoV PIs and we believe can be dosed twice daily without the requirement for ritonavir co-dosing based on Phase 1 clinical studies conducted to date.

Previous wording

ALG‑000184: Potential best‑in‑class small molecule CAM‑E for chronic hepatitis B virus infection

Current wording

Pevifoscorvir sodium: Potential best‑in‑class small molecule CAM‑E for chronic hepatitis B virus infection

Previous wording

In 2018, we in‑licensed a lead drug candidate (GLP‑26) and the associated IP for a CAM‑E from the laboratory of Professor Raymond Schinazi at Emory University. Our scientists optimized this lead drug candidate to discover the highly potent CAM‑E, ALG‑001075, which was further optimized to the prodrug ALG‑000184. ALG‑000184 has superior DMPK properties with enhanced absorption and high liver uptake, with a ~2-300-fold improvement in in vitro potency compared to other known CAMs. CAM‑Es are a class of small molecule antiviral agents that accelerate HBV capsid assembly and inhibit pgRNA encapsidation (1st MOA), resulting in empty viral capsids and lower circulating HBV DNA and RNA levels. CAM‑Es are also believed to regulate the establishment of cccDNA (2nd MOA), a major factor for the persistence of HBV infection which can be assessed by circulating HBV antigen levels (HBsAg, HBcrAg, and HBeAg). In clinical trials, competitor CAM‑Es have shown reductions in HBV DNA and RNA (1st MOA), but have rarely or inconsistently shown reductions in HBV antigens (2nd MOA). There have also been observations of the emergence of viral CAM-E drug resistance with competitor compounds.

Current wording

In 2018, we in‑licensed a lead drug candidate (GLP‑26) and the associated IP for a CAM‑E from the laboratory of Professor Raymond Schinazi at Emory University. Our scientists optimized this lead drug candidate to discover the highly potent CAM‑E, ALG‑001075, which was further optimized to the prodrug pevifoscorvir sodium. Based on pre-clinical data to date, pevifoscorvir sodium has superior DMPK properties with enhanced absorption and high liver uptake, with a ~2-300-fold improvement in in vitro potency compared to other known CAMs. CAM‑Es are a class of small molecule antiviral agents that accelerate HBV capsid assembly and inhibit pgRNA encapsidation (1st MOA), resulting in empty viral capsids and lower circulating HBV DNA and RNA levels. CAM‑Es are also believed to prevent the establishment of cccDNA (2nd MOA), a major factor for the persistence of HBV infection which can be assessed by circulating HBV antigen levels (HBsAg, HBcrAg, and HBeAg). In clinical trials, competitor CAM‑Es have shown reductions in HBV DNA and RNA (1st MOA), but have rarely or inconsistently shown reductions in HBV antigens (2nd MOA). There have also been observations of the emergence of viral CAM-E drug resistance with competitor compounds.

Previous wording

A multi-part Phase 1 study is ongoing, with the completed evaluation of the safety, tolerability, and pharmacokinetic profile of ALG-000184 in HVs. Additionally, a dose-ranging phase assessing the safety, pharmacokinetics, and antiviral activity of 10-300 mg doses of ALG-000184 administered over 28 days in untreated HBeAg+/- subjects with chronic HBV infection has also been completed. In these study phases, ALG‑000184 was found to be well tolerated with a favorable PK profile and demonstrated potentially best-in-class multi-log 10 HBV DNA and RNA reductions at all doses tested, as well as HBV surface antigen (HBsAg) reductions in a subset of HBeAg+ subjects receiving 100 mg or 300 mg of ALG-000184 (Hou et al, AASLD 2022). Based on the favorable profile observed with dosing up to 300 mg of ALG-000184 for 28 days, additional Phase 1 cohorts are currently underway to evaluate the risk-benefit profile of ALG-000184 at doses of 300 mg, with or without entecavir (ETV) therapy, for up to 96 weeks in HBeAg+and HBeAg- subjects with chronic HBV infection. Preliminary data from several of these cohorts (Hou et al., EASL 2025; Yuen et al., AASLD 2024, APASL 2025, EASL 2025) have been presented, showing that ALG‑000184, administered for up to 96 weeks, was well tolerated, exhibited a favorable PK profile, and demonstrated potentially best-in-class antiviral activity.

Current wording

A multi-part Phase 1 study is complete, with evaluation of the safety, tolerability, and pharmacokinetic profile of pevifoscorvir sodium in HVs. Additionally, a dose-ranging phase assessing the safety, pharmacokinetics (PK), and antiviral activity of 10‑300 mg doses of pevifoscorvir sodium administered over 28 days in untreated HBeAg+/- subjects with chronic HBV infection has also been completed. In these study phases, pevifoscorvir sodium was found to be well tolerated with a favorable PK profile and demonstrated potentially best-in-class multi-log 10 HBV DNA and RNA reductions at all doses tested, as well as HBV surface antigen (HBsAg) reductions in a subset of HBeAg+ subjects receiving 100 mg or 300 mg of pevifoscorvir sodium (Hou et al, AASLD 2022). Based on the favorable profile observed with dosing up to 300 mg of pevifoscorvir sodium for 28 days, additional Phase 1 studies evaluated the risk-benefit profile of pevifoscorvir sodium at doses of 300 mg, with or without entecavir (ETV) therapy, for up to 96 weeks in HBeAg+and HBeAg- subjects with chronic HBV infection. Preliminary data from several of these cohorts (Hou et al., EASL 2025; Yuen et al., AASLD 2024, APASL 2025, EASL 2025) have been presented, showing that pevifoscorvir sodium, administered for up to 96 weeks, was well tolerated, exhibited a favorable PK profile, and suggested potentially best-in-class potent and durable antiviral activity.

Previous wording

Data from this study following an oral daily dose of 300 mg ALG‑000184 monotherapy in HBeAg+ subjects demonstrated sustained HBV DNA suppression (<LLOQ (10 IU/mL, target detected (TD) or target not detected (TND)) in 6/10 (60%) subjects with chronic HBV infection at week 48 and 9/9 (100%) at week 96. Additionally, HBV DNA level continuously declined to < LLOQ (10 IU/mL, target not detected) in 5 of 9 subjects at Week 96. Data from the 300 mg ALG‑000184 HBeAg- monotherapy cohort demonstrated sustained HBV DNA suppression in all 11/11 (100%) subjects by Week 24. The HBV DNA suppression level was maintained in the ALG-000184 monotherapy cohort for up to 96 weeks, with further decline in HBV DNA to < LLOQ (10 IU/mL, target not detected) observed in all subjects (8/8) at Week 96. Importantly, no viral breakthrough was observed in any subject, and no known CAM resistant mutations were identified.

Current wording

subjects with chronic HBV infection at Week 48 and 9/9 (100%) at Week 96. Additionally, HBV DNA level continuously declined to < LLOQ (10 IU/mL, TND) in 5 of 9 subjects at Week 96. Data from the 300 mg pevifoscorvir sodium HBeAg- monotherapy cohort demonstrated HBV DNA suppression in all 11/11 (100%) subjects by Week 24 with the HBV DNA suppression level maintained for up to 96 weeks, with further decline in HBV DNA to < LLOQ (10 IU/mL, TND) observed in all subjects (8/8) at Week 96. Importantly, no viral breakthrough was observed in any subject, and no known CAM resistant mutations were identified.

Previous wording

Additionally, HBV RNA level achieved < LLOQ (10 copies/mL) in all HBeAg+ and HBeAg- subjects by Week 52 and Week 8, respectively. Furthermore, concurrent multi-log 10 reductions in HBV antigens (HBsAg, HBeAg, and HBcrAg) in HBeAg+ subjects and HBcrAg decline in HBeAg- subjects were observed, suggesting the potential inhibition of cccDNA establishment by CAM-E 2nd mechanism of action of ALG-000184.

Current wording

Additionally, HBV RNA level achieved < LLOQ (10 copies/mL) in all HBeAg+ and HBeAg- subjects by Week 52 and Week 6, respectively. Furthermore, concurrent multi-log 10 reductions in HBV antigens (HBsAg, HBeAg, and HBcrAg) in HBeAg+ subjects and HBcrAg decline in HBeAg- subjects were observed, suggesting the potential inhibition of cccDNA establishment by CAM-E 2nd mechanism of action of pevifoscorvir sodium.

Previous wording

Compared to Phase 3 studies with the current standard of care nucleos(t)ide analogs (NAs), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) (Buti et al., Lancet Gastro, 2016; Chen et al., Lancet Gastro 2016), these Phase 1 data to date suggest, subject to confirmation via further study, that ALG‑000184 treatment may be superior to NAs in HBeAg+/- subjects in achieving HBV DNA levels < LLOQ (10 IU/mL) after 48 weeks on treatment, which is the approvable endpoint for chronic suppressive therapy in chronic HBV infection (Food and Drug Administration (FDA) Guidance, Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment Guidance for Industry, April 2022 – Section III.B.1.a). We have received affirmative feedback from the FDA, the Committee for Medicinal Products for Human Use (CHMP: EU) and the National Medical Products Administration (NMPA: China) supporting subsequent studies utilizing the chronic suppressive therapy pathway for ALG-000184. These clinical studies, including the Phase 2 B-SUPREME study, will be conducted to test superiority to standard of care NA treatment (HBV DNA levels < LLOQ (10 IU/ml, target detected or target not detected) in HBeAG+ subjects and HBV DNA levels < LLOQ (10 IU/ml, target not detected) in HBeAg-subjects) after 48 weeks of monotherapy treatment. Furthermore, when combined with other mechanisms of action, including other candidates in our chronic HBV infection portfolio, ALG-000184 dosing regimens have the potential to contribute to achieving higher rates of functional cure, subject to testing such endpoint, as compared with currently approved agents.

Current wording

Compared to Phase 3 studies with the current standard of care nucleos(t)ide analogs (NAs), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) (Buti et al., Lancet Gastro, 2016; Chen et al., Lancet Gastro 2016), these Phase 1 data to date suggest, subject to confirmation via further study, that pevifoscorvir sodium treatment may be superior to NAs in HBeAg+/- subjects in achieving HBV DNA levels < LLOQ (10 IU/mL) after 48 weeks on treatment, which is the approvable endpoint for chronic suppressive therapy in chronic HBV infection (Food and Drug Administration (FDA) Guidance, Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment Guidance for Industry, April 2022 – Section III.B.1.a). We have received affirmative feedback from the FDA, the Committee for Medicinal Products for Human Use (CHMP: EU) and the National Medical Products Administration (NMPA: China) supporting subsequent studies utilizing the chronic suppressive therapy pathway for pevifoscorvir sodium. Our ongoing Phase 2 B-SUPREME study is being conducted to test superiority to standard of care NA treatment (HBV DNA levels <LLOQ (10 IU/ml, TD or TND) in HBeAg+ subjects and HBV DNA levels < LLOQ (10 IU/ml, TND) in HBeAg-subjects) after 48 weeks of monotherapy treatment. Furthermore, when combined with other mechanisms of action, including other candidates in our chronic HBV infection portfolio, pevifoscorvir sodium dosing regimens have the potential to contribute to achieving higher rates of functional cure, subject to testing such endpoint, as compared with currently approved agents.

Previous wording

Dosing of HBeAg+and HBeAg- subjects with ALG‑000184 in Phase 1 was recently completed and 96-week safety, PK, antiviral activity, and certain post-treatment data are expected to be presented at upcoming scientific conferences. In 2024, Aligos announced that the FDA cleared the Company’s investigational new drug application (IND) for a Phase 1 drug-drug interaction study, which has been completed.

Current wording

Dosing of HBeAg+and HBeAg- subjects with pevifoscorvir sodium in Phase 1 has been completed and the 96-week safety, PK, antiviral activity, and post-treatment data are expected to be presented at upcoming scientific conferences. In 2024, Aligos announced that the FDA cleared the Company’s investigational new drug application (IND) for a Phase 1 drug-drug interaction study, which has been completed.

Previous wording

The Phase 2 B-SUPREME (NCT04746183) study is designed as 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 currently untreated HBeAg+ and HBeAg- adult subjects with chronic HBV infection for 48 weeks. The primary endpoint in the HBeAg+ arm is HBV DNA <LLOQ (10 IU/mL, target detected (TD) or target not detected (TND)) and the primary endpoint in the HBeAg- arm is HBV DNA <LLOQ (10 IU/mL target not detected (TND)). The study is also evaluating safety, pharmacokinetics, and other secondary and exploratory biomarkers, including reductions in HBV antigens and other markers of HBV infection. The Phase 2 study began obtaining regulatory approvals, activating global sites, and screening subjects recently. Dosing is expected to commence in the coming weeks. The Company expects to announce interim data is projected in 2026, and topline data in 2027.

Current wording

The Phase 2 B-SUPREME study (NCT06963710) is designed as a randomized, double-blind, active-controlled multicenter study evaluating the safety and efficacy of pevifoscorvir sodium monotherapy compared with tenofovir disoproxil fumarate for 48 weeks in approximately 200 currently untreated HBeAg+ and HBeAg- adult subjects with chronic HBV infection. The primary endpoint in the HBeAg+ arm is HBV DNA <LLOQ (10 IU/mL, TD or TND) and the primary endpoint in the HBeAg- arm is HBV DNA <LLOQ (10 IU/mL, TND). The study is also evaluating safety, PK, and other secondary and exploratory HBV biomarkers, including reductions in HBV antigens and other markers of HBV infection. The Phase 2 study has obtained worldwide regulatory approvals, and is currently activating global sites, and enrolling subjects. The first subject was dosed in August 2025. Interim data is projected in both the first and second half of 2026 and topline data is anticipated in 2027.

Previous wording

We are also exploring additional ways to potentially treat patients with chronic HBV infection, including our antisense oligonucleotide (ASO) platform which utilizes novel monomers that could potentially reduce ASO toxicity and improve ASO liver to kidney ratio.

Current wording

We are also exploring additional ways to potentially treat patients with chronic HBV infection, including our antisense oligonucleotide (ASO) platform which utilizes novel monomers that could potentially reduce ASO toxicity and improve ASO liver to kidney ratios.

Previous wording

ALG‑055009: Potential best-in-class small molecule THR-β agonist for metabolic dysfunction-associated steatohepatitis

Current wording

ALG‑055009: Potential best-in-class small molecule THR-β agonist for obesity and metabolic dysfunction-associated steatohepatitis

Previous wording

MASH is a complex, chronic liver disease which is a leading cause of liver-related morbidity including cirrhosis, hepatocellular carcinoma, liver transplant, and end-stage liver disease. In 2024, the FDA approved resmetirom, a THR-β agonist, as the first drug for the treatment of MASH. However, additional agents in this class are needed to address remaining unmet needs, including the potential for improved efficacy and a more favorable risk-benefit profile. To achieve this, ALG-055009 has been purposefully designed to exhibit significantly greater potency (approximately 50-fold higher compared to resmetirom in head-to-head in vitro studies) and enhanced β selectivity, along with optimized pharmacologic properties to deliver an improved PK profile. We believe these advantages position ALG‑055009 as a strong candidate to become a best-in-class THR-β agonist.

Current wording

Obesity is a complex disease caused by an overabundance of body fat that increases the risk of other comorbidities, such as MASH. MASH is a complex, chronic liver disease which is a leading cause of liver-related morbidity including cirrhosis, hepatocellular carcinoma, liver transplant, and end-stage liver disease. In 2014, the first GLP-1 receptor agonist, liraglutide, was approved for weight loss and in 2024, the FDA approved resmetirom, a THR-β agonist, as the first drug for the treatment of MASH. However, additional agents in these classes are needed to address remaining unmet needs, including the potential for improved efficacy and a more favorable risk-benefit profile. To achieve this, ALG-055009 has been purposefully designed to exhibit significantly greater potency (approximately 50-fold higher compared to resmetirom in head-to-head in vitro studies) and enhanced β selectivity, along with optimized pharmacologic properties to deliver a potentially improved PK profile compared to other THR-β agonists. We believe these advantages position ALG‑055009 as a strong candidate to become a best-in-class THR-β agonist.

Previous wording

A first-in-human Phase 1 study of ALG‑055009 in HVs (oral single ascending doses (SAD)) and in subjects with hyperlipidemia (14 oral daily multiple ascending doses (MAD)) has been completed. Clinical data after single doses up to 4 mg and multiple doses up to 1 mg showed that ALG‑055009 was well tolerated, had dose proportional PK with low intersubject variability, and demonstrated expected thyromimetic effects (i.e., generally dose proportional increases in sex hormone binding globulin and decreases in various atherogenic lipids and thyroid hormones without any clinical evidence of thyroid dysfunction). We also evaluated relative bioavailability where we showed the soft gelatin capsules used in the Phase 2a study described below delivered similar exposures compared to the solution formulation used in the SAD/MAD parts of the Phase 1 study; we observed low intersubject PK variability and there was no evidence of a meaningful food effect.

Current wording

A first-in-human Phase 1 study of ALG‑055009 in MASH in HVs (oral single ascending doses (SAD)) and in subjects with hyperlipidemia (14 oral daily multiple ascending doses (MAD)) has been completed. Clinical data after single doses up to 4 mg and multiple doses up to 1 mg showed that ALG‑055009 was well tolerated, had dose proportional PK with low intersubject variability, and demonstrated expected thyromimetic effects (i.e., generally dose proportional increases in sex hormone binding globulin and decreases in various atherogenic lipids and thyroid hormones without any clinical evidence of thyroid dysfunction). We also evaluated relative bioavailability where we showed the soft gelatin capsules used in the Phase 2a study described below delivered similar exposures compared to the solution formulation used in the SAD/MAD parts of the Phase 1 study; we observed low intersubject PK variability and there was no evidence of a meaningful food effect.

Previous wording

0.9 mg) of ALG-055009 vs. placebo in 102 subjects with presumed MASH and liver fibrosis at stages 1-3 (F1-F3). The primary endpoint of this study was percent relative change in liver fat content by MRI-PDFF at Week 12. This study also evaluated the safety and PK of ALG-055009 treatment and its effect on multiple other efficacy biomarkers, including other non-invasive tests previously shown to be impacted by treatment with THR‑β agonists. We announced positive topline data from this study in 2024, demonstrating that ALG-055009 dose groups were well-tolerated and met the primary endpoint. Specifically, doses of 0.5 mg to 0.9 mg ALG-055009 demonstrated statistically significant reductions in liver fat at Week 12, with placebo-adjusted median relative reductions up to 46.2% as measured by MRI-PDFF. Up to 70% of subjects achieved ≥30% relative reduction in liver fat compared to baseline. Eighteen subjects who were on stable GLP-1 agonist therapy qualified for enrollment in the study, with liver fat content meeting the inclusion criteria of ≥10% at baseline as measured by MRI-PDFF. Notably, 11 of 14 subjects on stable GLP-1 agonists treated with ALG-055009 had liver fat decreases, whereas 4 of 4 subjects on stable GLP-1 agonists treated with placebo had increases in liver fat over the 12-week dosing period (Loomba et al, AASLD 2024).

Current wording

Based on these promising Phase 1 data, we conducted the Phase 2a HERALD study (NCT06342947) at sites across the United States. The study was a 12-week randomized, double-blind, placebo-controlled trial evaluating 4 doses (0.3 mg, 0.5 mg, 0.7 mg, and 0.9 mg) of ALG-055009 vs. placebo in 102 subjects with presumed MASH and liver fibrosis at stages 1-3 (F1-F3). The primary endpoint of this study was percent relative change in liver fat content by MRI-PDFF at Week 12. This study also evaluated the safety and PK of ALG-055009 treatment and its effect on multiple other efficacy biomarkers, including other non-invasive tests previously shown to be impacted by treatment with THR‑β agonists. We announced positive topline data from this study in 2024, demonstrating that ALG-055009 dose groups were well-tolerated and met the primary endpoint. Specifically, doses of 0.5 mg to 0.9 mg ALG-055009 demonstrated statistically significant reductions in liver fat at Week 12, with placebo-adjusted median relative reductions up to 46.2% as measured by MRI-PDFF. Up to 70% of subjects achieved ≥30% relative reduction in liver fat compared to baseline. Eighteen subjects who were on stable GLP-1 agonist therapy qualified for enrollment in the study, with liver fat content meeting the inclusion criteria of ≥10% at baseline as measured by MRI-PDFF. Notably, 11 of 14 subjects on stable GLP-1 agonists treated with ALG-055009 had liver fat decreases, whereas 4 of 4 subjects on stable GLP-1 agonists treated with placebo had increases in liver fat over the 12-week dosing period (Loomba et al, AASLD 2024).

Previous wording

In the Phase 2a study, ALG‑055009 demonstrated a favorable tolerability profile with no evidence of clinical hyper/hypothyroidism. Incidence of gastrointestinal-related treatment emergent adverse events were similar in ALG‑055009 dose groups compared to placebo. Specifically, similar rates of diarrhea were observed in ALG‑055009 dose groups compared to placebo, with no dose-response. Significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B, were also observed (Loomba et al, AASLD 2024).

Current wording

In the Phase 2a HERALD study, ALG‑055009 demonstrated a favorable tolerability profile with no evidence of clinical hyper/hypothyroidism. Incidence of gastrointestinal-related treatment emergent adverse events were similar in ALG‑055009 dose groups compared to placebo. Specifically, similar rates of diarrhea were observed in ALG‑055009 dose groups compared to placebo, with no dose-response. Significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B, were also observed (Loomba et al, AASLD 2024).

Previous wording

We are continuing to evaluate a variety of options to fund continued development, including potential out-licensing.

Current wording

We believe ALG-055009 warrants further development as a potential treatment for both obesity and MASH. We are continuing to evaluate a variety of options to fund continued development, including potential out-licensing.

Previous wording

Another area of focus is to develop drug candidates with pan-coronavirus antiviral activity, including against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. In this area of focus, we are exploring small molecule coronavirus 3CL protease inhibitors (PIs) in collaboration with the Rega Institute at Katholieke Universiteit Leuven (KU Leuven), the Center for Innovation and Stimulation of Drug Discovery (CISTIM) and the Centre for Drug Design and Discovery (CD3). This collaboration led to the discovery of ALG‑097558 which has completed a Phase 1 first-in-human evaluation in healthy volunteers and advanced into a clinical trial evaluating high-risk COVID-19 patients.

Current wording

Another area of focus is to develop drug candidates with pan-coronavirus antiviral activity, including against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. In this area of focus, we are exploring small molecule coronavirus 3CL protease inhibitors (PIs) in collaboration with the Rega Institute at Katholieke Universiteit Leuven (KU Leuven), the Center for Innovation and Stimulation of Drug Discovery (CISTIM) and the Centre for Drug Design and Discovery (CD3). This collaboration led to the discovery of ALG‑097558 which has completed a Phase 1 first-in-human evaluation in healthy volunteers and advanced into a clinical trial evaluating the compound in high-risk COVID-19 patients.

Previous wording

ALG‑097558 has been shown in preclinical studies to be at least 3-fold more potent than nirmatrelvir and other PIs in clinical development against a panel of SARS-CoV-2 variants (including Omicron). It also has demonstrated broad pan‑coronavirus activity, including against SARS-CoV-1 and MERS-CoV. In the first-in-human Phase 1 clinical study, single doses up to 2000 mg and multiple doses up to 800 mg Q12H for 7 days were well tolerated with an acceptable PK profile that suggests ritonavir boosting is not required. Furthermore, the absence of a clinically relevant DDI with midazolam suggests that ALG‑097558 can be co-administered with CYP3A4 substrates (NCT05840952). Based on these Phase 1 data (Wilkes et al., RespiDart, 2024), the projected efficacious dose range to treat SARS-CoV-2 is 200-600 mg ALG‑097558 Q12 x 5 days, without the need for ritonavir coadministration.

Current wording

ALG‑097558 has been shown in preclinical studies to be at least 3-fold more potent than nirmatrelvir and other PIs in clinical development against a panel of SARS-CoV-2 variants (including Omicron). It also has demonstrated broad pan‑coronavirus activity, including against SARS-CoV-1 and MERS-CoV. In the first-in-human Phase 1 clinical study, single doses up to 2000 mg and multiple doses up to 800 mg Q12H for 7 days were well tolerated with an acceptable PK profile that suggests ritonavir boosting may not be required. Furthermore, the absence of a clinically relevant DDI with midazolam suggests that ALG‑097558 may be able to be co-administered with CYP3A4 substrates (NCT05840952). Based on these Phase 1 data (Wilkes et al., RespiDart, 2024), the projected efficacious dose range to treat SARS-CoV-2 is 200-600 mg ALG‑097558 Q12 x 5 days, without the need for ritonavir coadministration.

Previous wording

ALG‑097558 began three additional 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‑19 patients evaluating ALG‑097558 as monotherapy or in combination with remdesivir (NCT04746183). Additionally, clinical studies evaluating PK in special populations (renal and hepatic impairment subjects; NIAID contract) are on-going (NCT06698549). NIAID is also sponsoring a drug‑drug interaction and relative bioavailability study in healthy volunteers that began dosing in the second quarter of 2025 (NCT06568861). We expect that future development of ALG‑097558, including ongoing Phase 2 enabling activities, will be funded by external sources, including public funding sources as described below.

Current wording

A Phase 2 study of ALG‑097558 began in 2024. The AGILE trial, a United Kingdom government-supported platform trial (MRC and Wellcome Trust funding), is sponsoring and performing a study in high‑risk COVID‑19 patients evaluating ALG‑097558 as monotherapy or in combination with remdesivir (NCT04746183). We expect that future development of ALG‑097558 will be funded by external sources, including public funding sources as described below.

Previous wording

Preclinical activities for our coronavirus program were partially funded through a grant from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern program through the Metropolitan AntiViral Drug Accelerator (MAVDA) consortium. Specific clinical and nonclinical studies for the ALG-097558 program and the follow up compound, are now also being funded with federal funds from the NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93023C00052. We filed an IND in the third quarter of 2024 and clinical studies in special populations were initiated in the second half of 2024 as part of this NIAID contract. We expect to receive approximately $15.3 million in funds across these two NIH awards and contracts to support these activities. To date, these funds have not been impacted by any changes at the NIH or NIAID. We are also seeking additional external funding (e.g., from governmental agencies) to support future studies as we advance ALG‑097558 for the treatment of COVID‑19 and future coronavirus pandemics.

Current wording

Preclinical activities for our coronavirus program were partially funded through a grant from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern program through the Metropolitan AntiViral Drug Accelerator (MAVDA) consortium. Specific clinical and nonclinical studies for the ALG-097558 program and the follow up compound, are now also being funded with federal funds from the NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93023C00052. We filed an IND in the third quarter of 2024. We expect to receive approximately $15.3 million in funds across these two NIH awards and contracts to support these activities. To date, these funds have not been impacted by any changes at the NIH or NIAID. We are also seeking additional external funding (e.g., from governmental agencies) and/or collaborations (e.g., platform trials) to support future studies as we advance ALG‑097558 for the treatment of COVID‑19 and future coronavirus pandemics.

Previous wording

Contract revenue includes recognition of revenue generated from research and development services under third-party contracts with customers. In order to record contract revenue, we utilize an input method to recognize revenue over time as costs are incurred.

Current wording

Customer revenue includes recognition of revenue generated from research and development services under third-party contracts with customers. In order to record customer revenue, we utilize an input method to recognize revenue over time as costs are incurred.

Previous wording

We expect our expenses to increase substantially in connection with our ongoing clinical development activities related to our chronic HBV infection drug candidate ALG‑000184. We rely substantially on third parties to conduct our discovery activities, nonclinical studies, clinical trials and manufacturing. We estimate research and development expenses based on estimates of services performed, and rely on third party contractors and vendors to provide us with timely and accurate estimates of expenses of services performed to assist us in these estimates. A portion of our research and development expenses are based on contractual milestones. Research and development costs consist primarily of costs incurred for the identification and development of our drug candidates through our technology platforms, which include:

Current wording

We expect our expenses to increase substantially in connection with our ongoing clinical development activities related to our chronic HBV infection drug candidate pevifoscorvir sodium. We rely substantially on third parties to conduct our discovery activities, nonclinical studies, clinical trials and manufacturing. We estimate research and development expenses based on estimates of services performed, and rely on third party contractors and vendors to provide us with timely and accurate estimates of expenses of services performed to assist us in these estimates. A portion of our research and development expenses are based on contractual milestones. Research and development costs consist primarily of costs incurred for the identification and development of our drug candidates through our technology platforms, which include:

Previous wording

We have incurred net losses and negative cash flows from operations in each year since our formation in February 2018. Our net income was $27.2 million for the six months ended June 30, 2025 and net loss was $29.8 million for the six months ended June 30, 2024, and our net losses were $131.2 million for the year ended December 31, 2024. We have had no revenue from product sales. As of June 30, 2025, we had an accumulated deficit of $590.8 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses over at least the next several years. Our net operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of our clinical trials and nonclinical studies and our other research and development expenses. We have no internal manufacturing capabilities or sales force and outsource a substantial portion of our clinical trial work to third parties.

Current wording

We have had no revenue from product sales, and it is uncertain when in the future we may generate product sales. We have no internal manufacturing capabilities or sales force, and we outsource a substantial portion of our clinical trial work to third parties. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses over at least the next several years. Our net operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of our clinical trials and nonclinical studies and our other research and development expenses.

Previous wording

Comparison of the three and six months ended June 30, 2025 and 2024

Current wording

Comparison of the three and nine months ended September 30, 2025 and 2024

Previous wording

The following table summarizes our operating expenses for the three and six months ended June 30, 2025 and 2024 (in thousands):

Current wording

The following table summarizes our operating expenses for the three and nine months ended September 30, 2025 and 2024 (in thousands):

Previous wording

There was no revenue recognized from collaborations for the three and six months ended June 30, 2025, due to the termination of the Merck collaboration agreement in the first quarter of 2024. We recognized $0.3 million as revenue from collaborations for the six months ended June 30, 2024.

Current wording

There was no revenue recognized from collaborations for the three and nine months ended September 30, 2025, due to the termination of the Merck collaboration agreement in the first quarter of 2024. We recognized $0.3 million as revenue from collaborations for the nine months ended September 30, 2024. We do not expect significant future revenue from collaborations at this time.

Previous wording

Revenue from customers decreased by $0.1 million and $0.5 million for the three and six months ended June 30, 2025, when compared to the same period in 2024. The decrease was due to the near completion of the original agreement with Amoytop and the start of the extension agreement.

Current wording

Revenue from customers decreased by $0.5 million and $1.0 million for the three and nine months ended September 30, 2025, when compared to the same period in 2024. The decrease was due to the near completion of the original agreement with Amoytop, a higher value contract, and the start of the extension agreement, which had a lower value. We do not expect significant future revenue from customers at this time.

Previous wording

Research and development expenses decreased by $7.1 million during the three months ended June 30, 2025, compared to the same period in 2024. The decrease in the three-month period was primarily due to a $7.6 million decrease in third-party expenses due to reduced clinical study costs as a result of the completion of the MASH Phase 2a clinical trial, partially offset by increased spend in the chronic HBV infection program. This was partially offset by a $0.3 million increase in travel and entertainment and a $0.2 million increase in facility and other expenses.

Current wording

Research and development expenses decreased by $1.8 million during the nine months ended September 30, 2025, compared to the same period in 2024. The decrease in the nine-month period was primarily due to a $2.0 million decrease in third-party expenses due to reduced clinical study costs in our Coronavirus program and as a result of the completion of the MASH Phase 2a clinical trial during this period, partially offset by increased spend in our pevifoscorvir sodium Phase 2a clinical trial which began in 2025. Further there was a $0.2 million increase in facility, travel and other expenses.

Previous wording

General and administrative expenses decreased by $0.8 million during the three months ended June 30, 2025, compared to the same period in 2024. This was primarily due to a $1.0 million decrease in third party expenses due to reduced legal and intellectual property spend, partially offset by a $0.2 million increase in facility, travel and entertainment costs.

Current wording

General and administrative expenses increased by $0.5 million during the three months ended September 30, 2025, compared to the same period in 2024. This was primarily due to a $0.4 million increase in third party expenses due to increased legal and intellectual property spend, and a $0.2 million increase in employee-related costs, partially offset by a $0.1 million increase in facility, travel and entertainment costs.

Previous wording

General and administrative expenses decreased by $2.4 million during the six months ended June 30, 2025, compared to the same period in 2024. This was primarily due to a $1.8 million decrease in third party expenses due to reduced legal and intellectual property spend. There was also a $0.6 million decrease in salary costs.

Current wording

General and administrative expenses decreased by $1.9 million during the nine months ended September 30, 2025, compared to the same period in 2024. This was primarily due to a $1.5 million decrease in third party expenses due to reduced legal and intellectual property spend. There was also a $0.4 million decrease in employee-related costs.

Previous wording

Interest and other income, net remained relatively flat during the three months ended June 30, 2025 as compared to the same period in the prior year. Interest and other income decreased by $0.7 million during the six months ended June 30, 2025 as compared to the same period in the prior year due primarily to a decrease in the accretion of short-term investments.

Current wording

Interest and other income, net remained relatively flat during the three months ended September 30, 2025 as compared to the same period in the prior year. Interest and other income decreased by $0.7 million during the nine months ended September 30, 2025 as compared to the same period in the prior year due primarily to a decrease in the accretion of short-term investments.

Previous wording

The change in fair value of 2023 common warrants was a decrease of $28.8 million and an increase of $47.1 million for the three and six months ended June 30, 2025 compared to the same period ended June 30, 2024. The change was due to a change in the fair value of the 2023 common warrants measured using the Black Scholes option pricing model remeasured at each reporting period, principally due to a change in the stock price between reporting periods.

Current wording

The change in fair value of 2023 common warrants was a decrease of $4.1 million and an increase of $43.0 million for the three and nine months ended September 30, 2025 compared to the same period ended September 30, 2024. The change was due to a change in the fair value of the 2023 common warrants measured using the Black Scholes option pricing model remeasured at each reporting period, principally due to a change in the stock price between reporting periods.

Previous wording

We have incurred net losses in each year since inception. Our net losses were $131.2 million for the year ended December 31, 2024 and $87.7 million for the year ended December 31, 2023. We had a net income of $27.2 million for the six months ended June 30, 2025, due to a gain resulting from the remeasurement of the 2023 Common Warrants. Without this gain, we would have a net loss. We have not generated any revenue from product sales or any other sources and have incurred significant operating losses. We have not yet commercialized any products and we do not expect to generate revenue from sales of any drug candidates for at least several years, if ever.

Current wording

We have incurred net losses in each year since inception. Our net losses were $4.3 million for the nine months ended September 30, 2025 and $131.2 million for the year ended December 31, 2024. We have not generated any revenue from product sales or any other sources and have incurred significant operating losses. We have not yet commercialized any products and we do not expect to generate revenue from sales of any drug candidates for at least several years, if ever.

Previous wording

Our primary use of cash is to fund operating expenses, which consist primarily of research and development costs related to our drug candidates and our discovery programs, and to a lesser extent, general and administrative expenditures. We expect our expenses to increase substantially in connection with our ongoing clinical development activities related to our chronic HBV infection drug candidate ALG‑000184, which we have initiated clinical trials, as well as our research and development of our other drug candidates.

Current wording

Our primary use of cash is to fund operating expenses, which consist primarily of research and development costs related to our drug candidates and our discovery programs, and to a lesser extent, general and administrative expenditures. Our current operating plan and projected cash outflows for the upcoming periods raise doubt about our ability to continue as a going concern for at least 12 months from the issuance of the financial statements. If we are successful with our ability to access additional funding, we expect our expenses to increase substantially in connection with our ongoing clinical development activities related to our chronic HBV infection drug candidate pevifoscorvir sodium, which we have initiated clinical trials, as well as our research and development of our other drug candidates.

Previous wording

In addition, we incur costs associated with operating as a public company. We expect that our expenses will increase substantially to the extent we:

Current wording

We expect that our expenses will increase substantially to the extent we:

Previous wording

During the six months ended June 30, 2024, operating activities utilized $42.2 million of cash, primarily resulting from our net loss of $29.8 million and net changes in operating assets and liabilities of $1.4 million, partially offset by non-cash charges of $11.1 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $1.4 million, consisting of a decrease of $4.8 million in accrued liabilities, a decrease of $1.3 million in operating lease liabilities, and a decrease in other assets of $0.3 million, partially offset by an increase of $4.3 million in accounts payable. The decrease in accrued liabilities was largely due to the bonus payments that occurred in the first quarter of 2024. The decrease in accounts payable is due to the timing of payments to vendors.

Current wording

During the nine months ended September 30, 2025, operating activities utilized $60.8 million of cash, primarily resulting from our net loss of $4.3 million, offset by net changes in operating assets and liabilities of $1.4 million, and non-cash charges of $55.1 million, driven by the $59.0 million gain as a result of remeasuring the 2023 Common Warrants. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $1.4 million, consisting of a decrease of $2.0 million in accrued liabilities, a decrease of $2.3 million in operating lease liabilities, partially offset by a decrease in other assets of $0.8 million, and an increase of $2.1 million in accounts payable. The decrease in accrued liabilities was largely due to the bonus payments that occurred in the first quarter of 2025, recorded on the balance sheet as of December 31, 2024. The increase in accounts payable is due to the timing of payments to vendors, with overall increased spend due in our pevifoscorvir sodium Phase 2a clinical trial.

Previous wording

During the six months ended June 30, 2025, operating activities utilized $36.4 million of cash, primarily resulting from our net income of $27.2 million, offset by net changes in operating assets and liabilities of $2.9 million, and non-cash charges of $60.7 million, driven by the gain as a result of remeasuring the 2023 Common Warrants. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $2.9 million, consisting of a decrease of $3.4 million in accrued liabilities, a decrease of $1.5 million in operating lease liabilities, partially offset by an increase of $0.4 million in deferred revenue, a decrease in other assets of $0.2 million, and an increase of $1.3 million in accounts payable. The increase in deferred revenue was due to the recognition of revenue from customers due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to the bonus payments that occurred in the first quarter of 2025. The increase in accounts payable is due to the timing of payments to vendors.

Current wording

During the nine months ended September 30, 2024, operating activities utilized $62.3 million of cash, primarily resulting from our net loss of $49.1 million, net changes in operating assets and liabilities of $4.6 million, and non-cash charges of $8.6 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $4.6 million, consisting of a decrease of $2.7 million in accrued liabilities, a decrease of $2.0 million in operating lease liabilities, an decrease of $0.7 million in deferred revenue, partially offset by an increase of $0.2 million in accounts payable and a decrease in other assets of $0.5 million. The decrease in deferred revenue from collaborations was due to the recognition of revenue from collaborations due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to the bonus payments that occurred in the first quarter of 2024. The decrease in accounts payable is due to the timing of payments to vendors.

Previous wording

During the six months ended June 30, 2025, investing activities used $83.5 million of cash, primarily due to $103.3 million of purchase of short-term investments, partially offset by $20.0 million related to maturities of short-term investments.

Current wording

During the nine months ended September 30, 2025, investing activities used $35.8 million of cash, primarily due to $125.5 million of purchase of short-term investments, partially offset by $90.0 million related to maturities of short-term investments.

Previous wording

During the six months ended June 30, 2024, investing activities used $48.6 million of cash, primarily due to $88.6 million of purchase of short-term investments, partially offset by $40.0 million related to maturities of short-term investments.

Current wording

During the nine months ended September 30, 2024, investing activities used $38.3 million of cash, primarily due to $108.1 million of purchase of short-term investments partially offset by $70.0 million related to maturities of short-term investments.