Aligos Therapeutics Presents Clinical Data for its NASH Program and Non-Clinical Data for its Chronic Hepatitis B Portfolio at AASLD’s The Liver Meeting® 2022 | small molecules

Aligos Therapeutics Presents Clinical Data for its NASH Program and Non-Clinical Data for its Chronic Hepatitis B Portfolio at AASLD’s The Liver Meeting® 2022 |  small molecules

Aligos Therapeutics Presents Clinical Data for its NASH Program and Non-Clinical Data for its Chronic Hepatitis B Portfolio at AASLD’s The Liver Meeting® 2022

ALG-055009, a THR-β agonist drug candidate in development as a treatment for NASH, demonstrated dose-dependent reductions in several atherogenic lipids and a favorable pharmacokinetic profile in subjects with hyperlipidemia

Aligos oral and poster presentations also collectively highlight new data from the company’s drug candidates targeting PD-L1 inhibition and the CAM-A (CAM-aberrant) mechanism for the treatment of chronic hepatitis B (CHB)

SOUTH SAN FRANCISCO, CA, USA I Nov 04, 2022 I Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical-stage biopharmaceutical company focused on developing novel therapies to address unmet medical needs in viral and liver diseases, today announced that the company will present several posters and an oral presentation at The Liver Meeting. ® (November 4-8, 2022), organized by the American Association for the Study of Liver Diseases (AASLD).

In particular, poster 2354 provides new data on the activity of ALG-055009, the Aligos thyroid hormone receptor beta (THR-β) agonist in development for nonalcoholic steatohepatitis (NASH). Multiple Ascending Dose (MAD) data from the ongoing Phase 1 study ALG-055009-301 (NCT05090111) demonstrate that treatment for 14 days in subjects with hyperlipidemia resulted in reduced levels of triglycerides, low-density lipoprotein (LDL) and apolipoprotein B in a generally dose-dependent manner. ALG-055009 was well tolerated and resulted in favorable dose-proportional pharmacokinetics with low inter-subject variability throughout the therapeutic range.

“We are pleased with the emerging clinical profile of ALG-055009,” said Lawrence Blatt, Ph.D., MBA, CEO and Chairman of the Board of Aligos. “THR-β agonists continue to have the potential to become a cornerstone therapy in the treatment of NASH, and ALG-055009 appears to compare favorably with other drugs in this class. In the future, we plan to evaluate its ability to reduce liver fat in NASH subjects over a twelve-week period in an internally or partnership-funded phase 2 study.”

Aligos oral and poster presentations at The Liver Meeting collectively highlight new data from the company’s drug candidates targeting chronic hepatitis B (CHB) and non-alcoholic steatohepatitis (NASH) and are available on the site Aligos website in Scientific presentations and conferences. The details of the presentation are described below.

Aligos has highlighted new Phase 1 clinical data on its CAM-E drug candidate, ALG-000184, in a separate press release.

presentation details

NASH

THR-β agonist

Title: Safety, pharmacokinetics, and pharmacodynamics of multiple ascending oral doses of ALG-055009, a thyroid hormone receptor beta agonist, in hyperlipidemic subjects.
Publication number: 2354
Presenter: Dr Hakim Charfi
Summary: See above.

chronic hepatitis B

PD-L1 inhibitor: small molecule

Title: Discovery of liver-targeted oral PDL1 small-molecule inhibitors for the treatment of chronic hepatitis B and liver cancers
Presentation number: 34890
Publication number: 26
Presenter: Tongfei Wu, Ph.D.
Summary: The authors rationally designed liver-targeted small-molecule oral PD-L1 inhibitors to localize T-cell activation to the liver and thus potentially mitigate systemic toxicity, in an effort to develop PD1/PD-L1 inhibitors. L1 better tolerated for patients with CHB. The lead molecules developed to date show in vivo efficacy similar to that of approved antibodies, but were more effective than antibodies in a liver metastatic tumor model.

PD-L1 inhibitor: siRNA

Title: Suppression of PD-L1 expression by a novel liver-targeting siRNA leads to possible restoration of immune responses against HBV
Poster number: 36189
Publication number: 1186
Presenter: Jin Hong, Ph.D.
Summary: Liver-targeted PD-L1 siRNA therapy can lead to restoration of immune responses against HBV and subsequent clearance of HBV infection, which is considered essential for the cure of CHB. Multiple siRNAs with subnanomolar PD-L1 mRNA inhibition CEfifty values ​​have been identified. Efforts are underway to identify siRNAs with higher efficiency of reducing PD-L1 expression as well as higher anti-HBV activity.

BED

Title: Non-PAH class I capsid assembly modulators have distinct profiles and a distinct mechanism of action
Poster number: 37007
Publication number: 1208
Presenter: Yannick Debing, Ph.D.
Summary: Non-PAH (heteroaryldihydropyrimidine) CAM-1 (CAM-A or CAM-aberrant) compounds ALG-005398 and ALG-006162 have a profile that is clearly distinct from known CAM-1 PAHs. The data presented here suggest that non-PAH CAM-1s may promote HBsAg reduction through a different mechanism than PAH CAM-1s. Since the optimized non-PAH CAM-1s have adequate ADME/toxicity profiles, they represent an attractive class of molecules for further development as part of potential functional cure regimens for CHB.

Title: HAP Class I capsid assembly modulators clear hepatitis B virus-infected hepatocytes through nucleus-dependent hepatocyte death and subsequent proliferation
Poster number: 36810
Publication number: 1202
Presenter: Dieudoneé Buh Kum, Ph.D.
Summary: PAH CAM-1 (CAM-A or CAM-aberrant) RG7907 in vivo and in vitro was shown to act through two mechanisms, possibly complemented by an immune response, resulting in a sustained loss of HBV-positive cells. First, RG7907 was shown to induce hepatitis B virus (HBV) core protein (HBc) aggregation and hepatocyte apoptosis in HBc-expressing cells. Second, compensatory proliferation of hepatocytes was shown to lead to further loss of AAV-HBV episomes. This represents an attractive mechanism for regimens aimed at introducing a functional cure in HCC.

siRNA

Title: Preclinical efficacy, pharmacokinetic profile, and pharmacokinetic/pharmacodynamic (PK/PD) correlation of ALG-125755, a GaINAc-conjugated siRNA, for functional cure of chronic hepatitis B
Poster number: 35097
Publication number: 1155
Presenter: Kusum Gupta
Summary: ALG-125755 demonstrates encouraging preclinical pharmacology, PK/PD properties, and a long half-life in the liver, predicting monthly or less frequent dosing in human subjects. A phase 1 study of ALG-125755 began dosing in healthy volunteers in October 2022.

About Aligos

Aligos Therapeutics, Inc. is a clinical-stage biopharmaceutical company that was founded in 2018 with a mission to become a world leader in the treatment of viral infections and liver disease. Aligos is focused on the discovery and development of targeted antiviral therapies for chronic hepatitis B (CHB) and coronaviruses, as well as leveraging its expertise in liver disease to create targeted therapies for non-alcoholic steatohepatitis (NASH). Aligos’ strategy is to leverage its team’s deep expertise and decades of drug development experience in liver diseases, particularly viral hepatitis, to rapidly advance its portfolio of potentially best-in-class molecules.

FONT: Aligos Therapeutics

Leave a Comment