ALG-020572 / Aligos Therap - LARVOL DELTA

Antisense oligodeoxynucleotides: the certain but limited efficacy and the uncovering mechanisms for the cure of chronic hepatitis B (PubMed, Zhonghua Gan Zang Bing Za Zhi) - "Particularly in the report of phase IIb clinical trial of Bepirovirsen (GSK3228836), approximately 9-10% patients with low baseline serum HBsAg (> 100 IU/ml & < 3 000 IU/ml) achieved functional cure after 24 weeks' of Bepirovirsen treatment. After reviewing the results of other clinical trials, one would be impressed to know that ALG-020572 (Aligos), RO7062931 (Roche) and GSK3389404 (GSK) all failed to sufficiently suppress serum HBsAg expression though the hepatocyte-targeted delivery of these ASOs were enhanced via N-acetyl galactosamine conjugation...Eventually the serum HBsAg declines in most participants and even disappears in a small fraction of patients with low baseline HBsAg level, via attack the infected hepatocytes evidenced by the aberrant elevation of ALT. Nevertheless, the functional cure of CHB remains a challenging issue and more efforts are needed."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=40 | Terminated | Sponsor: Aligos Therapeutics | Trial completion date: Feb 2023 ➔ Jul 2022 | Completed ➔ Terminated | Trial primary completion date: Feb 2023 ➔ Jul 2022; ALT flares suggestive of drug induced liver injury

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

A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Completed | N=112 ➔ 40 | Trial completion date: Jun 2022 ➔ Feb 2023 | Trial primary completion date: Jun 2022 ➔ Feb 2023

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

Incorporation of novel ASO chemistries significantly improves the potency and durability of HBV ASOs in the AAV-HBV mouse model (EASL-ILC 2022) - "GuNA and other novel BNAs improved the in vitro and in vivo activities of our lead ASO ALG-020572. Novel modifications of ALG-020576 significantly improved the in vivo depth and durability of HBsAg knockdown. Further investigations combining these chemistries are ongoing."

Preclinical • Hepatitis B • Hepatology

Safety, tolerability and pharmacokinetics of single ascending doses of ALG-020572, a GalNAc-conjugated antisense oligonucleotide, in healthy subjects (EASL-ILC 2022) - "ALG-020572 was safe and well tolerated with predictable PK properties when given to healthy subjects as single SC doses of up to 150 mg."

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

A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1 | N=112 | Active, not recruiting | Sponsor: Aligos Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2023 ➔ Jun 2022 | Trial primary completion date: Nov 2023 ➔ Jun 2022

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

"Aligos announced Tuesday it will discontinue development of ALG-020572 after a healthy volunteer was sent to the hospital to treat an adverse event. https://t.co/GR7HD2TEgk" (@endpts)

Adverse events • Clinical

Hepatitis B functional cure! Antisense Oligonucleotide (ASO) ALG-020572 Enters Phase 1 Clinical Study: First Patient Treated! [Google translation] (Bioon.com) - "Aligos Therapeutics...announced that the multiple ascending dose (MAD) portion of the clinical study ALG-020572-401 (NCT05001022) evaluating the antisense oligonucleotide (ASO) ALG-020572 has been evaluated in the first case of chronic hepatitis B (CHB) The patient was treated with medication...Results of this study and follow-up studies will be presented at future scientific meetings."

Trial status • Hepatitis B • Infectious Disease

Aligos Therapeutics Begins Dosing in Chronic Hepatitis B Patients in its Phase 1 Antisense Oligonucleotide Study (ALG-020572-401) (GlobeNewswire) - "Aligos Therapeutics, Inc...announced that the first chronic hepatitis B (CHB) patient has been dosed in the multiple ascending dose (MAD) portion of Study ALG-020572-401 (NCT05001022) which is evaluating antisense oligonucleotide (ASO) ALG-020572...Results of this and subsequent cohorts will be presented at a future scientific conference."

Trial status • Hepatitis B • Infectious Disease

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] 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 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] ALG-020572, A GALNAC-CONJUGATED ANTISENSE OLIGONUCLEOTIDE, DEMONSTRATES IN VIVO EFFICACY AND FAVORABLE PRECLINICAL PROFILE FOR THE TREATMENT OF CHRONIC HEPATITIS B (AASLD 2021) - "The efficacy, hepatocyte targeting and a favorable PK profile of ALG- 020572 following SC administration warrants its advancement into clinical development as a potential treatment for CHB."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Aligos Therapeutics Begins Dosing with Antisense Oligonucleotide Drug Candidate, ALG-020572, in Healthy Volunteers in a Phase 1 Proof-of-Concept Study (GlobeNewswire) - "Aligos Therapeutics, Inc...announced that the company has started dosing in the first cohort of healthy volunteers in Study ALG-020572-401 (NCT05001022). The trial is evaluating ALG-020572, a proprietary antisense oligonucleotide (ASO) therapeutic candidate that is designed to reduce circulating HBsAg (Hepatitis B surface antigen) levels."

Trial status • Hepatitis B • Infectious Disease

A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1; N=112; Recruiting; Sponsor: Aligos Therapeutics; Not yet recruiting ➔ Recruiting

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

Aligos Therapeutics Reports Recent Business Progress and Second Quarter 2021 Financial Results (GlobeNewswire) - "In addition, evaluation of ALG-000184, a small molecule class II capsid assembly modulator (CAM), was initiated in patients with CHB in April...Data from additional cohorts are expected to be presented at one or more scientific conferences in the second half of 2021...The initial CTA for our third CHB drug candidate, ALG-020572, an antisense oligonucleotide (ASO), was recently filed. We expect to begin evaluating ALG-020572 in HVs in the fourth quarter of 2021."

New trial • P1 data • Hepatitis B • Infectious Disease

A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects (clinicaltrials.gov) - P1; N=112; Not yet recruiting; Sponsor: Aligos Therapeutics

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

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

[VIRTUAL] ALG-020572, a next generation antisense oligonucleotide (ASO) with bridged nucleic acid chemistry, has a significantly improved preclinical profile (APASL 2021) - No abstract available

Preclinical

[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