ALG-125755 / Aligos Therap - LARVOL DELTA

Second generation HBV siRNAs with novel chemistries demonstrate improved profiles compared with ALG-125755 and other clinical stage siRNAs (EASL-ILC 2024) - "ALG-125839 with novel chemistries demonstrated improved activity and potential safety when compared with ALG-125755 and a Ph2 siRNA. Further studies of this novel compound are warranted."

Clinical • Hepatitis B • Hepatology • Inflammation • ASGR

A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=57 | Terminated | Sponsor: Aligos Therapeutics | N=120 ➔ 57 | Trial completion date: Dec 2025 ➔ Jun 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Jun 2023; Single doses demonstrated an acceptable safety profile and antiviral activity at all doses evaluated.

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

A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Aligos Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, pharmacokinetics, and antiviral activity of single ascending doses of ALG-125755, a GalNAc-conjugated small interfering RNA, in subjects with chronic hepatitis B (EASL-ILC 2023) - P1 | "Single SC doses of 50 mg ALG-125755 have been well tolerated to date in HBeAg negative CHB subjects with a safety and PK profile supporting further evaluation of higher dose levels."

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

Pharmacodynamic durability of ALG-125755, a GalNAc-conjugated siRNA, correlated with total and RNA induced complex (RISC) bound siRNA in mouse liver (EASL-ILC 2023) - "Binding of ALG-125755 to AGO-2 was demonstrated in vitro and in vivo, confirming that the mechanism of action for ALG-125755 is consistent with that of an siRNA. Pharmacodynamic response of HBsAg reduction and durability correlated with total siRNA and RISC-bound siRNA in mouse liver. The long half-life of the RISC-bound siRNA indicates that dosing in human could be less frequent than monthly dosing."

PK/PD data • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • AGO2

Aligos Therapeutics to Present Data from Chronic Hepatitis B and Hepatocellular Carcinoma Programs at the European Association for the Study of the Liver (EASL) Congress 2023 (GlobeNewswire) - "Aligos Therapeutics...announced that the company will present seven posters collectively highlighting data out of five of its liver disease programs at the European Association for the Study of the Liver (EASL) Congress 2023, taking place in Vienna, Austria, June 21 – 24, 2023....'We look forward to sharing additional detail at the time of the conference and further results throughout the year'."

Clinical data • Preclinical • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Infectious Disease • Liver Cancer • Oncology • Solid Tumor

ALG-125755, a GalNAc-siRNA Targeting Hepatitis B Virus (HBV) and Containing Novel Stabilization Chemistries Demonstrates Durable HBsAg Reduction in the AAV-HBV Mouse Model and No Significant Off-Target Liver Toxicity in the Humanized Liver Mouse Mode (APASL 2023) - "ALG-125755 demonstrated a favorable preclinical pharmacology, PK, and safety profile and has been advanced into clinic development for the functional cure of CHB. 705"

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, Tolerability and Pharmacokinetics (PK) of Single Ascending Doses of ALG-125755, a GalNAc-Conjugated Small Interfering RNA (siRNA), in Healthy Volunteers (HV) (APASL 2023) - P1 | "Single doses of up to 60 mg ALG-125755 to date have been well tolerated in HV with a safety and PK profile supporting further evaluation in CHB patients. 782"

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

A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Aligos Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

NONCLINICAL EFFICACY, PHARMACOKINETIC PROFILE AND PHARMACOKINETIC/PHARMACODYNAMIC (PK/PD) CORRELATION OF ALG-125755, A GALNAC-CONJUGATED siRNA, FOR FUNCTIONAL CURE OF CHRONIC HEPATITIS B (AASLD 2022) - "ALG-125755 demonstrated the desired preclinical pharmacology, PK properties, and long liver half-life that favors monthly or less frequent dosing in human. ALG-125755 is being advanced into clinical development for the functional cure of CHB."

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

A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Aligos Therapeutics

New P1 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

The HBV siRNA, ALG-125755, demonstrates a favourable nonclinical profile and significant and durable hepatitis B surface antigen reductions in the AAV-HBV mouse efficacy model (EASL-ILC 2022) - "ALG-125755 demonstrated high liver concentrations across species, and significant and durable HBsAg knockdown in the AAV-HBV mouse model. Further development of ALG-125755 as a potential best-in-class HBV siRNA is ongoing."

Preclinical • 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

[VIRTUAL] ALG-125755, a Small Interfering RNA (siRNA) Against Hepatitis B Virus (HBV) Effectively Inhibits Hepatitis B Surface Antigen (HBsAg) Secretion in HBV Cell Models and the AAV-HBV Mouse Model (EASL-ILC 2021) - "Multiple novel GalNAc conjugatedHBV siRNA sequences containing unique optimized stabilization patterns and novel chemistries demonstrated significant and durable HBsAg knockdown in the AAV-HBV mouse model. Among these, ALG-125755 has been selected for further development."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

[VIRTUAL] Combination drug interactions of hepatitis B virus ( HBV) small interfering RNA (siRNA) and antisense oligonucleotides (ASO) in vitro and in vivo (EASL-ILC 2021) - "The HBV siRNA, ALG-125755, in combination with the ASO, ALG-020572, demonstrated additive to minor synergy in vitro and in vivo. Further investigation of the strategy to combine HBV siRNA and ASO compounds in CHB clinical trials is warranted."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

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 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