ALG-020576 / Aligos Therap - LARVOL DELTA

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

[VIRTUAL] BEST-IN-CLASS ANTISENSE OLIGONUCLEOTIDES AGAINST HEPATITIS B VIRUS: NEXT GENERATION BRIDGED NUCLEIC ACID CHEMISTRIES SIGNIFICANTLY INCREASE IN VIVO EFFICACY AND REDUCE HEPATOTOXICITY IN MICE (AASLD 2021) - "BNA wing and nucleobase gap modifications of this sequence resulted in ALG-021467 and its GalNAc conjugated analog, ALG-020576, with EC50 values of 0.8 and 1.18 nM, respectively... We demonstrated that applying next generation BNA and nucleobase chemistries in LNA ASO gapmers can significantly reduce in vivo hepatotoxicity and improve the therapeutic index . These results suggest that application of these novel nucleotide chemistries could lead to best-in-class anti-HBV ASOs. Currently, novel ASO therapeutics using this approach are being advanced into clinical trials for CHB."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

[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