ALG-010133 / Aligos Therap - LARVOL DELTA

Safety, pharmacokinetics, and antiviral activity of the S-antigen Transport Inhibiting Oligonucleotide Polymers (STOPS) drug candidate ALG-010133 in subjects with chronic hepatitis B (EASL-ILC 2022) - "ALG-010133 was safe and well tolerated with predictable PK properties when given to CHB subjects as multiple SC doses of up to 400 mg. No meaningful HBsAg reduction was observed across all cohorts. Further clinical development of ALG-010133 has been discontinued."

Clinical • PK/PD data • Dermatology • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Failure • Novel Coronavirus Disease • Pruritus

A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1 | N=103 | Terminated | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Terminated; Lack of antiviral activity at the projected efficacious dose.

Trial termination • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1 | N=103 | Active, not recruiting | Sponsor: Aligos Therapeutics | Recruiting ➔ Active, not recruiting | N=164 ➔ 103 | Trial completion date: Aug 2022 ➔ Apr 2022 | Trial primary completion date: Aug 2022 ➔ Apr 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Aligos Halting Further Development of STOPS Drug Candidate, ALG-010133 (Yahoo Finance) - "Aligos Therapeutics, Inc...announced that it has halted further development of its STOPS™ drug candidate, ALG-010133, in development to address chronic hepatitis B (CHB). This decision is based on emerging data from the Phase 1 Study ALG-010133-101 that indicate that at the projected efficacious dose (400 mg, estimated to achieve liver exposures >3 x EC90 for HBsAg inhibition) there is no meaningful HBsAg reduction. Furthermore, higher doses levels (maximum feasible dose is 600 mg) that were planned to be evaluated in a subsequent cohort are very unlikely to reach the 1 log10 IU/mL HBsAg reduction level that Aligos had previously defined as necessary to advance the program...'Two drug candidates with these MOAs – ALG-000184 (CAM-2) and ALG-020572 (ASO) – are currently in the clinic and a third (ALG-125755, siRNA) is projected to be in the clinic mid-year 2022.'"

Discontinued • New trial • Hepatitis B • Infectious Disease

Aligos Presents Update of Chronic Hepatitis B Pipeline Portfolio at HEP DART 2021 (GlobeNewswire) - P1, N=156; NCT04536337; Sponsor: Aligos Therapeutics; "Aligos Therapeutics, Inc...announced that company management, will deliver an invited oral presentation at the 2021 HEP DART meeting, being held December 5 – 9, 2021 in Cabo San Lucas, Mexico...New data were shown at HEP DART from Aligos’ Phase 1b study (ALG-000184-201, NCT04536337) of the company’s CAM candidate ALG-000184...After once daily oral dosing for 28 days with 100 mg of ALG-000184, there was an average reduction of 4 log10 IU/mL of HBV DNA and >3 log10 copies/mL of HBV RNA...the presentation highlighted initial preclinical data on an oral small molecule PD-1/PD-L1 antagonist derived from the company’s internal discovery engine, for potential addition of this immune boosting mechanism to Aligos’ CHB portfolio."

P1 data • Preclinical • Hepatitis B • Infectious Disease

Aligos Therapeutics Presents Data for its Chronic Hepatitis B (CHB) and Nonalcoholic Steatohepatitis (NASH) Portfolio at The Liver Meeting 2021 (GlobeNewswire) - P1, N=156; NCT04536337; Sponsor: Aligos Therapeutics; "Aligos Therapeutics, Inc...will present several poster presentations at The Liver Meeting® 2021, hosted by the American Association for the Study of Liver Diseases (AASLD)...In both cohorts, ALG-000184 administration was associated with similar rapid, substantial reductions in HBV DNA and RNA through the 28-day period, with ≥75% and 100% of evaluable subjects achieving HBV DNA and RNA reductions below the lower limit of quantitation (LLOQ), respectively...Triple combinations of the siRNA ALG-125755 and STOPS ALG-010133 with the ASO ALG-020572 showed additive activity in reducing HBsAg and demonstrated a dose-dependent response with respect to the ASO."

P1 data • Preclinical • Hepatitis B • Infectious Disease

Aligos Therapeutics Reports Recent Business Progress and Third Quarter 2021 Financial Results (Yahoo Finance) - "S-Antigen Transport-Inhibiting Oligonucleotide Polymers (STOPS; ALG-010133)...We remain on track to unblind and share topline safety and viral kinetic data, including Hepatitis B S-antigen (HBsAg) data, from the first three cohorts in the first half of 2022. Capsid Assembly Modulator (CAM; ALG-000184)...Our Phase 1b dose range finding trial (NCT04536337) evaluating CHB subjects is ongoing...A poster describing the safety, PK, and antiviral activity of the 50 and 100 mg doses of ALG-000184 given for 28 days in HBeAg-negative CHB subjects will be presented at The Liver Meeting® (American Association for the Study of Liver Disease) later this month...Research and development (R&D) expenses for the three months ended September 30, 2021, were $28.1 million....the Company’s continued development and manufacturing of ALG-010133, ALG-000184 and ALG-020572 clinical trial activities..."

Commercial • Enrollment status • P1 data • PK/PD data • Hepatitis B • Infectious Disease

[VIRTUAL] TRIPLE COMBINATION OF ANTI-HEPATITIS B VIRUS DRUGS DEMONSTRATES SYNERGISTIC ACTIVITY IN VITRO (AASLD 2021) - "Future functional cure for CHB will require the combination of compounds with different mechanisms of action. Our HBV siRNA compound, ALG-125903, in combination with our ASO, ALG-020579 and STOPS molecule, ALG-010133, demonstrated synergistic activity in vitro . Further investigation of the strategy to combine HBV siRNA with ASO and STOPS compounds in human clinical trials is warranted ."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

[VIRTUAL] S-ANTIGEN TRANSPORT-INHIBITING OLIGONUCLEOTIDE POLYMERS, (STOPSTM) SEQUESTER CELLULAR PROTEINS TO REDUCE HEPATITIS B VIRUS S-ANTIGEN EXPRESSION AND INCREASE ITS PROTEASOMAL DEGRADATION (AASLD 2021) - "The STOPS molecule ALG-010133 is currently being studied in a Phase 1 clinical trial in CHB patients... Our results suggest a mechanism of action for STOPS molecules inhibition of HBV infection and HBsAg production that involves the sequestration of cellular factors needed to express and properly fold the S-antigen . Reduced levels of the cellular factors results in the increased ubiquitination and degradation of HBsAg."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • Targeted Protein Degradation • HSPA5

[VIRTUAL] IMPROVED LIVER CONCENTRATION AND ACTIVITY OF S-ANTIGEN TRANSPORT-INHIBITING OLIGONUCLEOTIDE POLYMERS (AASLD 2021) - " ALG-010000, ALG-010133, and ALG-010159 potently inhibited HBsAg secretion in vitro and demonstrated high liver concentrations in mice and NHP... GalNAc conjugation with an optimized linker design increased STOPS concentrations 3-fold in mouse and NHP livers. Furthermore, hepatocyte delivery correlated with antiviral activity in vitro. Improved liver concentrations and activity of GalNAc-conjugated STOPS indicates a potential to significantly reduce the effective antiviral dose for patients."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • ASGR

[VIRTUAL] safety, tolerability and pharmacokinetics (pk) of single and multiple doses of alg-010133, an s-antigen transport inhibiting oligonucleotide polymer (stops) for the treatment of chronic hepatitis b (EASL-ILC 2021) - "ALG-010133 was generally safe and well tolerated in HV as single and multiple SC doses up to 200 and 180 mg, respectively. The PK exposures achieved are expected to result in antiviral activity, supporting the ongoing evaluation in CHB patients."

Clinical • PK/PD data • Dermatology • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pain

Aligos Therapeutics Announces Pipeline Update and Upcoming Presentations at the European Association for the Study of the Liver’s Digital International Liver Congress 2021 (GlobeNewswire) - "Five scientific posters to be presented at upcoming EASL ILC meeting; All 4 Aligos CHB development candidates continue to advance – STOPS™ molecule and CAM drug candidates are currently being evaluated in CHB subjects - ASO and siRNA drug candidates are on track to enter clinical development in H2 2021 and H1 2022, respectively; Antiviral activity data from at least one cohort of CHB patients for ALG-010133 and ALG-000184 expected to be presented in H2 2021....We expect to present preliminary data from these Phase 1b studies in H2 2021. Once Phase 1b studies are completed, we plan to advance these drug candidates into Phase 2 studies in H2 2022...and are on track to start Phase 1 trials in H2 2021, and H1 2022, respectively."

New P1 trial • New P2 trial • P1 data • Preclinical • Hepatitis B • Infectious Disease

Aligos Therapeutics to Present Phase 1 Safety and Pharmacokinetic Data for STOPS Molecule Drug Candidate ALG-010133 and Several Nonclinical Chronic Hepatitis B Programs at the European Association for the Study of the Liver’s Digital International Liver Congress 2021 (GlobeNewswire) - P1, N=164; NCT04485663; Sponsor: Aligos Therapeutics; "First clinical data presented for ALG-010133, which is in development for S-antigen reduction in chronic hepatitis B (CHB) patients; Presentations include nonclinical data from 3 other CHB programs...ALG-010133 was generally safe and well tolerated in HVs when given as single and multiple (3 weekly) subcutaneous doses of up to 200 and 180 mg, respectively...In vitro, ALG-000111 demonstrated sub-nanomolar potency, sustained antiviral activity and significant HBV DNA knockdown. The compound’s prodrug form, ALG-000286, showed strong in vivo antiviral activity in an AAV-HBV mouse model as measured by declines in HBV DNA...Aligos’ siRNA candidate ALG-125755 and of Aligos’ ASO candidate ALG-020572 were evaluated for any additive or synergistic effects with respect to S-antigen knockdown, both in vitro and in vivo."

P1 data • Preclinical • Hepatitis B • Infectious Disease

Aligos Therapeutics Reports Recent Business Progress and First Quarter 2021 Financial Results (GlobeNewswire) - "Research and development (R&D) expenses for the three months ended March 31, 2021, were $22.9 million compared with $17.3 million for the same period of 2020. The increase in R&D expenses for this comparative period is primarily attributable to increased expenses related to the Company’s continued development of ALG-010133 and ALG-000184 clinical trial activities, as well as increases in salaries and employee-related expenses and preclinical programs."

Commercial • Hepatitis B • Infectious Disease

Aligos Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Recent Business Highlights (GlobeNewswire) - "'During 2020, we became both a well-financed public company, via our $167.2 million IPO, as well as a clinical stage company by advancing our first two CHB assets, ALG-010133 and ALG-000184, into the clinic. This year is on track to be similarly impactful for Aligos as we expect to generate important proof of activity data in CHB patients for both ALG-010133 and ALG-000184'...Enrollment of CHB patients is ongoing. The study is evaluating 12 weeks of once weekly subcutaneous ALG-010133...Safety and antiviral data from the initial cohort(s) is expected in the second half of 2021....Screening in CHB patients has commenced. The study is evaluating 28 days of once daily oral dosing of ALG-000184 or placebo...Safety and antiviral data from the initial cohort(s) expected in the second half of 2021."

Enrollment status • Financing • P1 data • Hepatitis B • Infectious Disease

Aligos Therapeutics Begins Dosing with STOPS Molecule Drug Candidate, ALG-010133, in First Cohort of Chronic Hepatitis B Patients in a Phase 1 Proof-of-Concept Study (GlobeNewswire) - "Aligos Therapeutics, Inc...announced that the company has started dosing in the first cohort of chronic hepatitis B (CHB) patients in the ongoing ALG-010133-101 study (NCT04485663). This trial is evaluating ALG-010133...which was developed to reduce viral S-antigen (or HBsAg) levels in CHB patients...'We expect to begin reporting safety, pharmacokinetic, and antiviral activity data for ALG-010133 from the initial patient cohorts of this study in the second half of 2021.'"

P1 data • Trial status • Hepatitis B • Infectious Disease

[VIRTUAL] Preclinical Efficacy and Pharmacokinetics of ALG-010133, an S- Antigen Transport-inhibiting Oligonucleotide Polymer (STOPS™) for the Treatment of Chronic Hepatitis B (CHB) (APASL 2021) - No abstract available

PK/PD data • Preclinical • Hepatitis B • Hepatology • Infectious Disease

[VIRTUAL] THE S-ANTIGEN TRANSPORT-INHIBITING OLIGONUCLEOTIDE POLYMER (STOPS™) ALG-010133 DEMONSTRATES A FAVORABLE PRECLINICAL PROFILE FOR THE TREATMENT OF CHRONIC HEPATITIS B (AASLD 2020) - "The combination of PK properties enabling SC administration and a favorable safety profile has allowed ALG-010133 to advance into clinical development to be evaluated as a potential treatment for CHB."

Preclinical • Hepatitis B • Hepatology • Infectious Disease

[VIRTUAL] -ANTIGEN TRAFFIC-INHIBITING OLIGONUCLEOTIDE POLYMERS (STOPS) EFFECTIVELY INHIBIT HEPATITIS B SURFACE ANTIGEN (HBsAg) SECRETION IN BOTH HEPATITIS B VIRUS (HBV) CELL LINES AND HBV INFECTED CELLS (AASLD 2020) - "ALG-010133 demonstrated robust, pan-genotypic inhibition of HBsAg release in multiple cell lines and infected liver cells, with enhanced activity compared to REP-2139. ALG-010133 inhibited HBsAg from the partial HBV genome integrated PLC/PRF 5 cell line, indicating the potential for reducing HBsAg in CHB patients with a high degree of HBV integration."

Preclinical • Hepatitis B • Hepatology • Infectious Disease

[VIRTUAL] DEVELOPMENT OF A BEST-IN-CLASS HBV ASO, ALG-020572, FOR THE TREATMENT OF CHRONIC HEPATITIS B (AASLD 2020) - "Both ASOs are significantly more potent than GSK32288361 in the AAV-HBV model. We explored the benefits of combining the two ASOs as well as combining the ASOs with other anti-HBV agents including the nucleos(t)ide analogs (NA) tenofovir and entecavir (ETV), the Capsid Assembly Modulator (CAM), ALG-0010752, parent of ALG-0001843 and the STOPSTM molecule, ALG-0101334... Compared with a single ASO, a 1:1 combination of ALG-020572 and ALG-020576 offers enhanced in vivo potency, better genotypic coverage, a higher resistance barrier and a greater capacity to retain efficacy after HBV genome integration events. This regimen can also be combined with other anti-HBV agents."

Hepatitis B • Hepatology • Infectious Disease

[VIRTUAL] Combination drug interactions of hepatitis B virus (HBV) S-antigen transport - inhibiting oligonucleotide polymers in vitro (EASL-ILC-I 2020) - "Combination of STOPs and ASOs exhibited the greatest potential for synergy with compound-dependent synergy volumes ranging from 343.05 uM2% (ALG-010133and ALG- 020002) to 3.87 uM2% (ALG-010093 and ALG-020205)... Future functional cure for CHB will require a combination of compounds with different mechanisms of action. STOPs demonstrate an in vitro antiviral profile that suggests they may become an important component of functional cure combination therapy. To this end, our STOP compounds are currently advancing towards combination clinical trials in CHB."

Preclinical • Hepatitis B • Hepatology • Infectious Disease

A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1; N=164; Recruiting; Sponsor: Aligos Therapeutics; Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Infectious Disease

A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1; N=164; Not yet recruiting; Sponsor: Aligos Therapeutics

Clinical • New P1 trial • Hepatitis B • Infectious Disease