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 HBV infection, 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 drug development and medicinal chemistry in liver and viral diseases, resulting in three potential best‑in‑class drug candidates.

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 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 CHB, 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, 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 THR‑β agonist for MASH with enhanced pharmacologic properties 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 coronavirus 3CL PI which is at least 3-fold more potent in cell-based assays of coronavirus infection than other approved CoV PIs and 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 MASH and obesity, 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 in subjects with presumed MASH. Recently presented nonclinical data suggests synergistic fat mass loss in combination with incretin receptor agonists in diet induced obese (DIO) mice. 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 HBV infection

Current wording

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

Previous wording

Our primary area of focus seeks to enhance the viral suppression and rate of functional cure for chronic HBV infection, which often results in life-threatening conditions such as cirrhosis, end-stage liver disease, and the most common form of liver cancer, HCC. To achieve this, we are developing a portfolio of differentiated chronic HBV infection drug candidates, including a small molecule CAM that results in the production of empty viral capsids and small molecule inhibitors of the Programmed Cell Death Ligand 1 (PD‑1/PD-L1) interaction.

Current wording

Our primary area of focus seeks to enhance the viral suppression and rate of functional cure for chronic HBV infection, which often results in life-threatening conditions such as cirrhosis, end-stage liver disease, and the most common form of liver cancer, hepatocellular carcinoma (HCC). To achieve this, we are developing a portfolio of differentiated chronic HBV infection drug candidates, including a small molecule CAM that results in the production of empty viral capsids.

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 300 mg ALG000184 (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 (Agarwal et al., EASL 2024; Yuen et al., AASLD 2024) have been presented, showing that ALG‑000184, administered for up to 92 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. Data from these cohorts (Yuen et al., AASLD 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 the 300 mg ALG‑000184 monotherapy cohort with up to 92 weeks in HBeAg+ and up to 84 weeks in HBeAg- subjects demonstrated sustained HBV DNA suppression (<LLOQ <10 IU/mL) in 7/7 (100%) HBeAg+ subjects with chronic HBV infection at week 84 and sustained HBV DNA suppression in all (11/11) HBeAg- subjects by Week 24. Importantly, no viral breakthrough was observed in any subject, and no known CAM resistant mutations were identified. At week 48, data from the 300 mg ALG-000184 monotherapy cohort demonstrated sustained HBV DNA suppression (<LLOQ <10 IU/mL) in 6/10 (60%) HBeAg+ subjects with chronic HBV infection and sustained HBV DNA suppression in all (11/11) HBeAg- subjects by Week 24. In addition, 91% (10/11) HBeAg- subjects achieved HBV DNA below the lower limit of detection (LLOD <4.29 IU/mL).

Current wording

Data from this study following an oral daily dose of 300 mg pevifoscorvir sodium 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, TND) in 5 of 10 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 8/9 subjects (89%) at Week 96. Importantly, no viral breakthrough was observed in any subject, and no known CAM resistant mutations were identified.

Previous wording

Compared to Phase 3 studies with the current standard of care 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 indicate 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 CHB (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 supportive feedback from the FDA regarding chronic suppressive therapy with ALG-000184, along with the Committee for Medicinal Products for Human Use (CHMP; EU) and the National Medical Products Administration (NMPA; China). Subsequent clinical studies of ALG‑000184 will be conducted to show superiority to standard of care NA treatment (HBV DNA levels < LLOQ ) after 48 weeks of treatment. Furthermore, when combined with other mechanisms of action, such as Amoytop’s mipeginterferon alfa-2b, a well-established immunomodulator, and other candidates in our chronic HBV infection portfolio (as described below), ALG-000184 dosing regimens have the potential to contribute to achieving higher rates of functional cure than with currently approved agents. Dosing of HBeAg+ and HBeAg- subjects with ALG‑000184 ± ETV in Phase 1 will continue through 2025 and 96-week safety, PK, and antiviral activity data will be presented at upcoming scientific conferences. In October 2024, Aligos announced that the FDA cleared the Company’s investigational new drug application (IND) for a Phase 1 drug-drug interaction study, and Phase 2 enabling activities are ongoing with the study expected to begin in mid-2025.

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. Chronic suppressive therapy of HBV DNA levels is a validated approval pathway 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

ALG‑055009: Potential best-in-class small molecule THR-β agonist for MASH

Current wording

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

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 therapies may address 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). In this same study, 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

Based on these promising Phase 1 data, we initiated 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.

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. Phase 2b enabling activities are underway, with expected completion in the middle of 2025. We are also assessing potential Phase 2b clinical trial study designs with key opinion leaders. We are evaluating a variety of options to fund continued development, including potential out-licensing.

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

ALG‑097558: Potential best-in-class small molecule ritonavir-free pan-coronavirus protease inhibitor

Current wording

ALG‑097558: Potential best-in-class small molecule ritonavir-free protease inhibitor for pan-coronavirus

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 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 HVs and advanced into a clinical trial evaluating the compound in high-risk COVID-19 patients.

Previous wording

ALG‑097558 has been shown 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 indicates ritonavir boosting is not required and absence of a clinically relevant DDI with midazolam, suggesting ALG‑097558 can be co-administered with CYP3A4 substrates. 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 preclinical studies. 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 shown to be appropriate for co-administration 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. Additionally, clinical studies evaluating PK in special populations (renal and hepatic impairment subjects; NIAID contract) are on-going. NIAID is also sponsoring a drug‑drug interaction and relative bioavailability study in healthy volunteers expected to start dosing in the second quarter of 2025. 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 standard and 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 $13.8 million in funds across these two NIH awards and contracts to support these activities. We are also seeking additional external funding (e.g., from governmental agencies) to support future studies (e.g., Phase 2) 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

Collaboration revenue includes recognition of our upfront payments pursuant to the Merck Original Agreement and First Amendment. In order to record collaboration revenue, we utilize an input method to recognize revenue over time as costs are incurred.

Current wording

Collaboration revenue included recognition of our upfront payments pursuant to an agreement and amendment with Merck Sharp & Dohme Corp, that were terminated in prior years. In order to record collaboration revenue, we utilized an input method to recognize revenue over time as costs were incurred.

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 rely substantially on third parties to conduct our discovery activities, nonclinical studies, clinical trials and manufacturing. We primarily 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

costs associated with in-process research and development, including license fees and milestones paid to third-party collaborators for technologies with no alternative use;

Current wording

costs associated with in-process research and development, including license fees and milestones paid to third-party collaborators for technologies;

Previous wording

General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our executive, finance, corporate and business development and administrative functions. General and administrative expenses also include legal fees relating to patent and corporate matters; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; and facility-related expenses, which include direct depreciation costs and allocated expenses for rent and maintenance of facilities and other operating costs not otherwise classified as research and development costs.

Current wording

General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our executive, finance, corporate, legal and business development and administrative functions. General and administrative expenses also include legal fees relating to patent and corporate matters; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; and facility-related expenses, which include direct depreciation costs and allocated expenses for rent and maintenance of facilities and other operating costs not otherwise classified as research and development costs.

Previous wording

Interest and other income, net comprises interest income, and other income, net. Interest income, net primarily consists of interest earned on our cash, cash equivalents, and investments. Other income, net consists primarily of accretion/amortization of investments and foreign currency exchange gains/losses.

Current wording

Interest and other income, net comprises interest income, net and other income, net. Interest income, net primarily consists of interest earned on our cash, cash equivalents, and investments. Other income, net includes investments and foreign currency gains/losses.

Previous wording

The change in fair value of Common Warrants includes the remeasurement of the Common Warrants using the Black Scholes option pricing model at each reporting period, and the change in fair value is recorded in earnings.

Current wording

The change in fair value of 2023 Common Warrants includes the remeasurement of the 2023 Common Warrants using the Black Scholes option pricing model at each reporting period.

Previous wording

Since our inception in 2018, we have not recorded any U.S. federal or state income tax benefits for the net losses we have incurred in any year or for our earned research and development tax credits, due to our uncertainty of realizing a benefit from those items. As of December 31, 2024, we had federal net operating loss (NOL) carryforwards of $41.8 million available to reduce taxable income and these NOLs can be carried forward indefinitely. We have state NOL carryforwards of $90.7 million as of December 31, 2024, available to reduce future state taxable income, which expire at various dates beginning in 2043. As of December 31, 2024, we also had federal and state research and development tax credit carryforwards of $1.9 million and $1.2 million, respectively. The federal research and development tax credit carryforwards begin to expire in 2043, while the state research and development tax credit carryforwards can be carried forward indefinitely. As of December 31, 2024, the Company had $8.4 million of Australian NOL carryforwards and $0.6 million of Australian research and development tax credit carryforwards available. The Australian NOL carryforwards and research and development tax credits have no expiration date.

Current wording

Since our inception in 2018, we have not recorded any U.S. federal or state income tax benefits for the net losses we have incurred in any year or for our earned research and development tax credits, due to our uncertainty of realizing a benefit from those items. As of December 31, 2025, we had federal net operating loss (NOL) carryforwards of $92.5 million available to reduce taxable income and these NOLs can be carried forward indefinitely. We have state NOL carryforwards of $105.7 million as of December 31, 2025, available to reduce future state taxable income, which expire at various dates beginning in 2043. As of December 31, 2025, we also had federal and state research and development tax credit carryforwards of $3.5 million and $2.2 million, respectively. The federal research and development tax credit carryforwards begin to expire in 2043, while the state research and development tax credit carryforwards can be carried forward indefinitely. As of December 31, 2025, the Company had $3.2 million of Australian NOL carryforwards and $0.7 million of Australian research and development tax credit carryforwards available. The Australian NOL carryforwards and research and development tax credits have no expiration date.

Previous wording

Under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an “ownership change” (generally defined as a greater than 50 percentage point change (by value) in its equity ownership over a rolling three-year period), our ability to use our pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income may be limited. We performed a Code Section 382 analysis in 2023 and determined there was an ownership change that resulted in Section 382 limitations, the impact of which is reflected in the financial statements. We performed a Code Section 382 analysis in 2024 and determined no further ownership change.

Current wording

Under Sections 382 and 383 of the Internal Revenue Code (Code), and corresponding provisions of state law, if a corporation undergoes an “ownership change” (generally defined as a greater than 50 percentage point change (by value) in its equity ownership over a rolling three-year period), our ability to use our pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income may be limited. We performed a Code Section 382 analysis in 2025 and determined no further ownership change.

Previous wording

Revenue from collaborations was $0.3 million for the year ended December 31, 2024, compared to $9.3 million for the year ended December 31, 2023, a decrease of $9.0 million. This is due to the completion of the Original Agreement with Merck in the first quarter of 2023, leaving the Amended collaboration agreement with Merck to continue in the year ended December 2023. The Amended collaboration agreement with Merck ended in May 2024.

Current wording

Revenue from collaborations was $0.3 million for the year ended December 31, 2024. There was no collaboration revenue for the year ended December 31, 2025. This is due to the completion of the amended collaboration agreement with Merck ended in May 2024.

Previous wording

Revenue from customers was $3.6 million for the year ended December 31, 2024, compared to $6.2 million for the year ended December 31, 2023, a decrease of $2.6 million, primarily due to the agreement with Amoytop, which was signed in 2023. Refer to footnote 12, Revenue from Contracts with Customers for further information.

Current wording

Revenue from customers was $2.2 million for the year ended December 31, 2025, compared to $3.6 million for the year ended December 31, 2024, a decrease of $1.4 million, primarily due to the collaboration and license agreement with Amoytop, the collaboration portion of which ended in November 2025. Refer to Note 10, Revenue from Contracts with Customers for further information.

Previous wording

We track direct external research and development expenses on a program-specific basis (CHB, coronaviruses, MASH and early-stage programs). The following table summarizes these research and development costs, in thousands:

Current wording

We track direct external research and development expenses on a program-specific basis (chronic HBV infection, MASH, coronaviruses and early-stage programs). The following table summarizes these research and development costs (in thousands):

Previous wording

Research and development expenses were $70.3 million for the year ended December 31, 2024, compared to $73.0 million for the year ended December 31, 2023, a decrease of $2.8 million. This is primarily due to a decrease of $4.2 million in employee-related costs, of which $1.8 million related to stock-based compensation. There was also a decrease of $0.3 million in depreciation and a decrease of $0.7 million in facility expenses. Offsetting this was an increase of $2.4 million in third-party expenses mainly related to increases in our ongoing CAM and MASH clinical study activities and related expenditures.

Current wording

Research and development expenses were $69.5 million for the year ended December 31, 2025, compared to $70.3 million for the year ended December 31, 2024, a decrease of $0.8 million. This is primarily due to a decrease of $1.8 million in third-party expenses due to increased government funds received for the coronavirus program which offset related costs. There was also a decrease of $0.2 million in depreciation. Offsetting this were increases of $0.4 million in employee-related costs, $0.4 million in facility expenses, and $0.4 million in travel and recruiting expenses.

Previous wording

General and administrative expenses were $22.8 million for the year ended December 31, 2024, compared to $30.6 million for the year ended December 31, 2023, a decrease of $7.8 million. This is due to a decrease of $4.2 million of third-party expenses primarily due to reduced legal and IP spend, a decrease of $3.0 million of employee-related costs, of which $2.0 million related to stock-based compensation, and a decrease of $1.3 million in facility and depreciation expenses. This was partially offset by an increase of $0.7 million in travel and recruiting costs.

Current wording

General and administrative expenses were $20.7 million for the year ended December 31, 2025, compared to $22.8 million for the year ended December 31, 2024, a decrease of $2.1 million. This is due to a decrease of $2.1 million of third-party expenses primarily due to reduced legal and IP spend, and a decrease of $0.3 million in facility expenses. This was partially offset by an increase of $0.1 million in depreciation and $0.2 million in travel and recruiting costs.

Previous wording

Interest income, net was $1.7 million for the year ended December 31, 2024 compared to $4.3 million for the year ended December 31, 2023, a decrease of approximately $2.6 million, primarily due to an decrease in market interest rates and a lower average investment balance.

Current wording

Interest income, net was $2.2 million for the year ended December 31, 2025 compared to $1.7 million for the year ended December 31, 2024, an increase of approximately $0.5 million, primarily due to a higher average investment balance.

Previous wording

Other income, net was an income of $2.7 million for the year ended December 31, 2024 compared to expense of $0.9 million for the year ended December 31, 2023, a difference of $3.6 million. The difference was due to an increase in the accretion of short-term investments.

Current wording

Other income, net was an income of $1.8 million for the year ended December 31, 2025 compared to income of $2.7 million for the year ended December 31, 2024, a decrease of $1.0 million. The difference was due to a decrease in the accretion of short-term investments.

Previous wording

The change in fair value of Common Warrants was an expense of $46.1 million for the year ended December 31, 2024 compared to an expense of $2.2 million for the year ended December 31, 2023, an increase of $44.0 million. The increase was due to a change in the fair value of the Common Warrants measured using the Black Scholes option pricing model remeasured at each reporting period.

Current wording

The change in fair value of 2023 Common Warrants was an income of $60.2 million for the year ended December 31, 2025 compared to an expense of $46.1 million for the year ended December 31, 2024, a difference of $106.3 million. The increase 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.

Previous wording

We have incurred net losses and negative cash flows from operations in each year since our formation in February 2018. Our net losses were $131.2 million and $87.7 million for the years ended December 31, 2024 and 2023, respectively. We have had no revenue from product sales. 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 and negative cash flows from operations in each year since our formation in February 2018. Our net losses were $24.2 million and $131.2 million for the years ended December 31, 2025 and 2024, respectively. We have had no revenue from product sales. 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

In October 2023, we completed a PIPE offering and entered into a securities purchase agreement (the "2023 Securities Purchase Agreement") pursuant to which we issued 1,257,168 shares of our common stock, par value $0.001 per share, pre-funded warrants to purchase an aggregate of 3,242,018 shares of our common stock (the “2023 Pre-Funded Warrants”), and common warrants to purchase an aggregate of 2,249,680 shares of our common stock (the “2023 Common Warrants,” and together with the 2023 Pre-Funded Warrants, the "2023 Warrants"). Each 2023 Warrant is exercisable for one share of common stock. The Company received gross proceeds of $92.1 million, and after deducting the placement agent fees and expenses and offering costs, net proceeds were $86.2 million.

Current wording

In October 2023, we completed a PIPE offering and entered into a securities purchase agreement (the 2023 Securities Purchase Agreement) pursuant to which we issued 1,257,168 shares of our common stock, par value $0.0001 per share, pre-funded warrants to purchase an aggregate of 3,242,018 shares of our common stock (the 2023 Pre-Funded Warrants), and common warrants to purchase an aggregate of 2,249,680 shares of our common stock (the 2023 Common Warrants, and together with the 2023 Pre-Funded Warrants, the 2023 Warrants). Each 2023 Warrant is exercisable for one share of common stock. We received gross proceeds of $92.1 million, and after deducting the placement agent fees and expenses and offering costs, net proceeds were $86.2 million.

Previous wording

In February 2025, we entered into a securities purchase agreement (the Securities Purchase Agreement) with certain investors names therein (the Purchasers) pursuant to which we issued (i) 2,103,307 shares of Common Stock, consisting of 1,427,000 shares of voting Common Stock and 676,307 shares of non-voting Common Stock, (ii) pre‑funded warrants (the Pre-Funded Warrants) to purchase up to an aggregate of 1,922,511 shares of voting Common Stock, and (iii) accompanying common warrants (the Common Warrants and, together with the Pre-Funded Warrants, the Warrants) to purchase up to an aggregate of 2,012,909 shares of voting Common Stock. Each Warrant is exercisable for one share of common stock (the 2025 Private Placement). We received gross proceeds of approximately $105.0 million. In connection to the 2025 Private Placement, we also entered into a registration rights agreement with the Purchasers, pursuant to which we agreed to register for resale the shares of common stock sold to the Purchasers, as well as the shares of common stock underlying the warrants sold to the Purchasers, on the terms set forth therein. We also entered into a registration rights agreement with Baker Brothers Life Sciences, L.P. (together with its affiliates, the Lead Investor), pursuant to which we agreed to file a resale registration statement with the Securities and Exchange Commission following demand by the Lead Investor to register the resale of shares of Common Stock and any Common Stock issued or issuable upon the exercise or conversion of non-voting Common Stock and any of our other securities held by the Lead Investor.

Current wording

In February 2025, we entered into a securities purchase agreement (the 2025 Securities Purchase Agreement) with certain investors named therein (the Purchasers) pursuant to which we issued (i) 2,103,307 shares of common stock, consisting of 1,427,000 shares of voting common stock and 676,307 shares of non-voting common stock, (ii) pre‑funded warrants (the 2025 Pre-Funded Warrants) to purchase up to an aggregate of 1,922,511 shares of voting common stock, and (iii) accompanying common warrants (the 2025 Common Warrants and, together with the 2025 Pre-Funded Warrants, the 2025 Warrants) to purchase up to an aggregate of 2,012,909 shares of voting common stock. Each Warrant is exercisable for one share of common stock (the 2025 Private Placement). We received gross proceeds of approximately $105.0 million. In connection to the 2025 Private Placement, we also entered into a registration rights agreement with the Purchasers, pursuant to which we agreed to register for resale the shares of common stock sold to the Purchasers, as well as the shares of common stock underlying the 2025 Warrants sold to the Purchasers, on the terms set forth therein. We also entered into a registration rights agreement with Baker Brothers Life Sciences, L.P. (together with its affiliates, the Lead Investor), pursuant to which we agreed to file a resale registration statement with the SEC following demand by the Lead Investor to register the resale of shares of common stock and any common stock issued or issuable upon the exercise or conversion of non-voting common stock and any of our other securities held by the Lead Investor.

Previous wording

As of December 31, 2024, we had cash, cash equivalents and investments of $56.9 million. As of December 31, 2024, we had an accumulated deficit of $618.0 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

As of December 31, 2025, we had cash, cash equivalents and investments of $77.8 million. As of December 31, 2025, we had an accumulated deficit of $642.2 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.

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 CHB drug candidate ALG-000184, which we have initiated clinical trials, as well as our research and development of our other drug candidates within our MASH and coronavirus programs.

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. We expect our expenses to increase substantially in connection with our ongoing clinical development activities related to our chronic hepatitis B drug candidate pevifoscorvir sodium, which has an ongoing Phase 2 clinical trial, as well as our research and development of our other drug candidates within our MASH and coronavirus programs.

Previous wording

In addition, we continue to incur additional costs associated with operating as a public company following our IPO in October 2020. 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: